| SARS-CoV-2 | binds to | ACE2 receptors (count: 3) | |
|---|---|
| 7 Furthermore, SARS-CoV-2 binds to ACE2 receptors in 10-20 fold higher affinity than SARS-CoV binds to the same receptors.
-- reference not found! | |
| 18 COVID-19 has spread rapidly since it was first identified in Wuhan and has been shown to have a wide spectrum of severity as SARS-CoV-2 binds to ACE2 receptors in 10-20 fold higher affinity than SARS-CoV binds to the same receptors.
-- Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population. medrxiv. 2020-03-10. | |
| COVID-19 has spread rapidly since it was first identified in Wuhan and has been shown to have a wide spectrum of severity as SARS-CoV-2 binds to ACE2 receptors in 10-20 fold higher affinity than SARS-CoV binds to the same receptors.
-- reference not found! | |
| SARS-CoV-2 | uses ACE2 as | receptor (count: 3) | |
| It has been proved that 93 SARS-CoV-2 uses ACE2 as a viral receptor for entry process 2,3 .
-- Evidence for gastrointestinal infection of SARS-CoV-2. medrxiv. 2020-02-20. | |
| It has been proved that SARS-CoV-2 uses ACE2 as a viral receptor for entry process.
-- reference not found! | |
| It has been proved that SARS-CoV-2 uses ACE2 as a viral receptor for entry process [2] .
-- Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020-03-03. | |
| SARS-CoV-2 | bind to | ACE2 (count: 2) | |
| In summary, the above findings suggest that SARS-CoV-2 and SARS-CoV bind to human ACE2 with similar affinities and hence may have similar transmissibility.
| |
| Recent researches speculated that SARS-CoV-2 could also bind to ACE2, and this was verified by computational docking and ELISA measurement 24, 25 .
-- reference not found! | |
| deterioration | diffusion of | COVID-19 (count: 2) | |
| medRxiv preprint the diffusion and deterioration of COVID-19 were inhibited quickly and effectively over China.
| |
| To estimate optimally the effects of Chinese strategies on controlling the diffusion and deterioration of COVID-19 in China, we performed model fitting and calculated the time at which the growth speed of the cumulative number of confirmed patients reached the maximum.
| |
| 2019-nCoV | use ACE2 as | receptor (count: 2) | |
| Initial structural modeling suggest that the 2019-nCoV may be able to use human ACE2 as a receptor, although its affinity m be reduced relative to the epidemic SARS-CoV strains [35] .
-- Return of the Coronavirus: 2019-nCoV. Viruses. 2020. | |
| Previous studies have uncovered several receptors that different coronaviruses bind to, such as ACE2 for SARS-CoV 29 and CD26 for MERS-CoV. 30 Our molecular modelling showed structural similarity between the receptor-binding domains of SARS-CoV and 2019-nCoV. Therefore, we suggest that 2019-nCoV might use ACE2 as the receptor, despite the presence of amino acid mutations in the 2019-nCoV receptor-binding domain.
| |
| N82 | contact with | F486 of SARS-CoV-2 S protein (count: 2) | |
| From the structure stimulation, we identified N82 in ACE2 show closer contact with F486 of SARS-CoV-2 S protein compared with M82 of ACE2.
-- reference not found! | |
| We concluded that N82 in ACE2 showed closer contact with F486 of SARS-CoV-2 S protein than M82 of ACE2.
-- reference not found! | |
| corresponding site | is in | SARS-CoV-2 S protein (count: 1) | |
| For 3 of these discontinuous B cell epitopes there was a partial mapping, with at least one site having an identical residue at the corresponding site in the SARS-CoV-2 S protein (Table 5) .
| |
| 20 Fifth | pathophysiology of | SARS-CoV-2 infecting through ACE2 receptor associated with COVID-19 seen in patients directly caused by SARS-CoV-2 (count: 1) | |
| 20 Fifth, the pathophysiology of SARS-CoV-2 infecting the lungs and intestines through the ACE2 receptor and TMPRSS2 or the acquired immunodeficiency (CD4 cells below 200 cells/mm 3 ) associated with COVID-19 (the severe or critical cases) seen in some patients directly or indirectly caused by SARS-CoV-2 is not understood, and further research and observation are needed.
-- Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population. medrxiv. 2020-03-10. | |
| we | focused | our analysis on interface segments of SARS-CoV-2 spike RBD 190 interacting with ACE2 from species (count: 1) | |
| In the current study, we 189 focused our analysis on the interface segments of SARS-CoV-2 spike RBD 190 interacting with ACE2 from different species by estimating interaction 191 energy profiles.
| |
| ACE2 analysis | targeting | animal reservoir of SARS-CoV-2 (count: 1) | |
| For model animals where Kd values are very low, ACE2 analysis 210 may play a key role in targeting the main animal reservoir of SARS-CoV-2.
| |
| it | is of | value focus on sequence mutation in S protein for SARS-CoV-2 evolution (count: 1) | |
| Therefore, it is of great value to focus on the sequence mutation and conformation change in S protein for SARS-CoV-2 evolution in a finely established model, aiming to explain the related change of COVID-19.
| |
| position | is in | S protein of SARS-CoV-2 (count: 1) | |
| Homology modeling clearly revealed the position of F1-3 sites in S protein of SARS-CoV-2 ( Fig 5A) .
| |
| SARS-CoV-2-ACE2 complex | contains | number (count: 1) | |
| The SARS-CoV-2-ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| COVID-19 virus | enters host cell by | RBD binding to host cell ACE2 receptor (count: 1) | |
| Similar to the SARS-2002 virus, the COVID-19 virus enters the host cell by RBD binding to the host cell ACE2 receptor (7, 11, 12) .
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| we | construct | contact maps for RBD-ACE2 interfaces for COVID-19 (count: 1) | |
| To investigate these interface residues, we construct and overlay the contact maps for the RBD-ACE2 interfaces for COVID-19 and SARS-2002 (Fig.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| We | attribute difference to | interaction of COVID-19 with middle of ACE2 helix (count: 1) | |
| We attribute this difference to the unique interaction of COVID-19 at position K417 with the middle of the N-terminal ACE2 helix, thus serving as an anchor site to the receptor (Fig.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| contribution | is observed in | cryoEM structure of COVID-19 spike protein bound (count: 1) | |
| The contribution of K417 to ACE2 binding is observed in a recent cryoEM structure of the COVID-19 spike protein bound to ACE2 (17) .
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| We | superimposed | MD snapshots on submitted to PDB x-ray structure of COVID-19-ACE2 complex (count: 1) | |
| We superimposed several MD snapshots on the recently submitted to the PDB x-ray structure (6VW1, resolution 2.7Å) of COVID-19-ACE2 complex.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| COVID-19 | creates | interaction patch with middle of ACE2 helix (count: 1) | |
| COVID-19 also creates a new interaction patch with the middle of the N-terminal ACE2 helix(Fig.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| contacts | were found for | RBD-ACE2 of COVID-19 (count: 1) | |
| COVID-19 has a significantly higher number of well-defined contact pairs compared to SARS-2002: 52 vs. 28 contacts (with 44 and 20 unique pairs, excluding the ones with similar CFs) were found for RBD-ACE2 of the COVID-19 and SARS-2002, respectively(Fig.
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| contact | is with | ACE2 vs. fraction of trajectory frames for COVID-19 (count: 1) | |
| A) Numbers of RBD residues in contact with ACE2 vs. the fraction of trajectory frames for COVID-19 (blue) and SARS-2002 (red). (
-- The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. biorxiv. 2020-03-12. | |
| SARS-CoV-2 | uses | ACE2 protein (count: 1) | |
| SARS-CoV-2 uses human ACE2 protein as their receptors [4] , which explains its similarly high transmissibility.
| |
| We | identified | 8 point muta-215 tion sites on S protein from cohort of 68 2019-nCoV samples 216 (count: 1) | |
| We identified 8 point muta-215 tion sites on S protein from a cohort of 68 2019-nCoV samples 216
-- reference not found! | |
| D 2019-nCoV spike protein point mutations | are | present (count: 1) | |
| D) Eight 2019-nCoV spike protein point mutations are present in a cohort of 68 viral samples.
-- reference not found! | |
| B 2019-nCoV S protein | is in | up position with Discotope2 (count: 1) | |
| We scanned 3D structures of modeled (A) and experimentally solved (B) 2019-nCoV S protein in the up position with Discotope2 to assess potential antibody binding sites (B-cell epitopes).
-- reference not found! | |
| 2019-nCoV | uses ACE2 as | its receptor 5-8 (count: 1) | |
| Protein structural analyses revealed that 2019-nCoV had a similar receptor-binding domain to that of SARS-CoV, directly binding to angiotensin converting enzyme II (ACE2), strongly suggesting that 2019-nCoV uses ACE2 as its receptor 5-8 .
| |
| 2019-nCoV | binds to | receptor ACE2 on surface (count: 1) | |
| In this study, we identified that teicoplanin could inhibit the entry of HIV-1-2019-nCoV-S pseudoviruses with the IC 50 value of 1.66 uM. During the invasion phase, 2019-nCoV first binds to the receptor ACE2 on the surface of host cells.
-- Teicoplanin potently blocks the cell entry of 2019-nCoV. biorxiv. 2020-02-13. | |
| 2019-nCoV virus | enters | endosome of cell (count: 1) | |
| Subsequently, the 2019-nCoV virus enters the early endosome of the cell through endocytosis or macropinocytosis.
-- Teicoplanin potently blocks the cell entry of 2019-nCoV. biorxiv. 2020-02-13. | |
| teicoplanin | prevents | 2019-nCoV S protein activation (count: 1) | |
| Our work indicates that both TMPRSS2 and cathepsin L are required for 2019-nCoV entrance, and teicoplanin potently prevents the 2019-nCoV S protein activation by directly inhibiting the enzymatic activity of cathepsin L (Figure 4) 27 .
-- Teicoplanin potently blocks the cell entry of 2019-nCoV. biorxiv. 2020-02-13. | |
| 2019-nCoV | utilize ACE2 as | 31 (count: 1) | |
| A recent study showed that 2019-nCoV is able to utilize ACE2 as an entry receptor in ACE2-expressing cells [31] , suggesting potential drug targets for therapeutic development.
-- Network-based Drug Repurposing for Human Coronavirus. medrxiv. 2020-02-05. | |
| SARS-CoV-2 S trimer | dominate in | 31 conformation distinguished from prefusion conformation (count: 1) | |
| Cryo-electron 30 microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a 31 unique conformation distinguished from the classic prefusion conformation of 32 coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral 33 membrane.
-- reference not found! | |
| prefusion SARS-CoV-2 S trimer | was | engineered (count: 1) | |
| https://doi.org/10.1101/2020.03.16.994152 doi: bioRxiv preprint worthy noted that the compared prefusion SARS-CoV-2 S trimer was engineered with 216 site-directed mutations to stabilize prefusion conformation and expressed in 239F cells.
-- reference not found! | |
| SARS-CoV-2 spike | retains | 298 prefusion conformation (count: 1) | |
| The SARS-CoV-2 spike expressed in insect cells predominantly retains a unique 298 early prefusion conformation, which was repeatable in at least three batches of samples 299 and is ascribed to two possible reasons -native aa sequence used in the S ectodomain The copyright holder for this preprint (which was not peer-reviewed) is the .
-- reference not found! | |
| SARS-CoV-2 S proteins 200 | of structures is | we (count: 1) | |
| EM structures of SARS-CoV-2 S proteins 200 To examine the structure of the trimeric S ectodomain with native sequence, we 201 prepared cryo-EM grids using the Ni-NTA purified S proteins and collected 1,513 202 electron micrograph movies.
-- reference not found! | |
| antigenicity 330 | find | prefusion conformation for SARS-CoV-2 spike (count: 1) | |
| 329 In conclusion, we obtain three kinds of S proteins showing excellent antigenicity 330 and find an early prefusion conformation for SARS-CoV-2 spike.
-- reference not found! | |
| d | BLASTing | motif binding domain of SARS-CoV-2 S protein (count: 1) | |
| d) BLASTing the motif binding domain of the SARS-CoV-2 S protein and the SARS-CoV S protein. (
-- reference not found! | |
| SARS-CoV-2 S protein | of motif is | RBM (count: 1) | |
| We also focused on the receptor-binding motif (RBM) of the SARS-CoV-2 S protein, which attaches to the ACE-2 protein for entry into the human cell (20) .
-- reference not found! | |
| We | align | RBM sequence of SARS-CoV-2 S protein (count: 1) | |
| We used BLAST to align the RBM sequence of the SARS-CoV-2 S protein with that of SARS-CoV, and found there is a relatively poor conservation between the two S proteins (Fig.
-- reference not found! | |
| design | should start with | SARS-CoV-2 S protein de novo (count: 1) | |
| Therefore, antibody-based therapeutic design should start with the SARS-CoV-2 S protein de novo.
-- reference not found! | |
| SARS-CoV-2 RBD | has | binding affinity to human ACE2 protein (count: 1) | |
| 9 measured the SARS-CoV-2 RBD's binding affinity to human ACE2 protein to be 15.2 nM, which is comparable to previously published affinity data for SARS-CoV spike protein 19 .
| |
| SARS-CoV-2 virus | infects cells | binding to ACE2 with affinities (count: 1) | |
| The above experimental results are consistent with our structure modeling analysis, which indicates that SARS-CoV-2 virus likely infects human cells through similar mechanisms as SARS-CoV virus by binding to human ACE2 with comparable affinities, and hence may possess similar transmissibility.
| |
| SARS-CoV-2 RBD-ACE2 complex structure | was | optimized (count: 1) | |
| The SARS-CoV-2 RBD-ACE2 complex structure was constructed base on the optimized SARS-CoV RBD-ACE2 complex structure using DS and was also optimized by Rosetta Relax.
| |
| RBD structures | is in | SARS-CoV-2 RBD-ACE2 complex model (count: 1) | |
| B. Conformational comparison between the RBD-ACE2 complex structures for SARS-CoV-2 and SARS-CoV. The RBD and ACE2 structures in the SARS-CoV-2 RBD-ACE2 complex model are shown as orange and pink tubes, respectively.
| |
| C. Distinct interaction patterns | is in | SARS-CoV-2 RBD-ACE2 interfaces (count: 1) | |
| C. Distinct interaction patterns in the SARS-CoV-2 and SARS-CoV RBD-ACE2 interfaces.
| |
| 2019-nCoV | use ACE2 as for | SARS-CoV (count: 1) | |
| The relatively high degree of sequence identity for the RBD is consistent with the view that 2019-nCoV, like SARS-CoV, may use ACE2 as its host cell receptor, as for SARS-CoV (Hoffmann et al.,
| |
| we | built | set for 2019-nCoV S protein (count: 1) | |
| Considering this, we built a first set of models for the 2019-nCoV S protein based on each of the above-mentioned structures ( Supplementary Fig.
| |
| S protein sequence | compare | characteristics of 2019-nCoV (count: 1) | |
| Taking an alternative approach, the S protein sequence of 2019-nCoV was submitted to two To better compare the predicted structural characteristics of the 2019-nCoV, we also performed homology modeling of four S proteins from Bat-CoVs belonging to lineage B in our phylogenetic analysis, that showed to be closely related to 2019-nCoV. The modeled S proteins from the Bat-author/funder.
| |
| their impact | is in | 2019-nCoV S protein function (count: 1) | |
| Despite amino acid variability, no major changes in the secondary structures and the overall folding of the proteins were observed among the modeled S structures of these viruses, suggesting a conserved organization for all the S proteins of the lineage B including the 2019-nCoV. Nevertheless, differences at the flexible loops in both domains were observed, and their impact in the 2019-nCoV S protein function must be further studied.
| |
| 2019-nCoV S protein models | based on | Betacoronavirus structures (count: 1) | |
| 2019-nCoV S protein models based on Betacoronavirus structures.
| |
| 2019-nCoV S protein models | were | built (count: 1) | |
| The 2019-nCoV S protein models were built based on the structure of HCoV-HKU1, MHV, MERS-CoV and SARS-CoV. The amino acid homology (red) and differences (blue) are noted.
| |
| they | may bind to | replication complex components of 2019-nCoV (count: 1) | |
| However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction.
| |
| ganciclovir | bind to | three subunits of replication complex of 2019-nCoV (count: 1) | |
| Also, ganciclovir was predicted to bind to three subunits of the replication complex of the 2019-nCoV: RNA-dependent RNA polymerase (Kd 11.91 nM), 3'-to-5' exonuclease (Kd 56.29 nM), and RNA helicase (Kd 108.21 nM).
| |
| inhibitor N3 | bind SARS-CoV-2 3CL pro with | Figure S4 (count: 1) | |
| indicates that the developed inhibitor N3, 6 which is a covalent inhibitor derived from non-covalent inhibitors against SARS can also bind SARS-CoV-2 3CL pro with a similar binding conformation ( Figure S4 ).
-- AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2. biorxiv. 2020-03-08. | |
| ACE2 receptor | has | has identified as 442 potential receptor for COVID-19 (count: 1) | |
| The human ACE2 receptor has also been identified as the 442 potential receptor for COVID-19 and represents a potential target for treatment [42, 43] .
| |
| Spike S protein | proteins of | SARS-CoV-2 (count: 1) | |
| Spike (S) protein, one of the main structural proteins of SARS-CoV-2, binds angiotensin-converting enzyme 2 (ACE2) protein of the host cell membrane to fuse into the cell for nucleic acid replication just similar to SARS-CoV [5] .
-- Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection. medrxiv. 2020-03-03. | |
| we | used | SARS-CoV-2 spike fusion assay (count: 1) | |
| Therefore, we herein 34 used a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that 35 SARS-CoV-2 showed plasma membrane fusion capacity superior to that of 36 SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core 37 of the HR1 and HR2 domains in SARS-CoV-2 S protein S2 subunit, revealing that 38 several mutated amino acid residues in the HR1 domain may be associated with 39 enhanced interactions with HR2 domain.
| |
| EK1C4 | was | 43 fusion inhibitor against SARS-CoV-2 S membrane fusion (count: 1) | |
| We previously developed a pan-coronavirus 40 fusion inhibitor, EK1, which targeted HR1 domain and could inhibit infection by 41 divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. We 42 then generated a series of lipopeptides and found that the EK1C4 was the most potent 43 fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and 44 pseudovirus infection with IC 50 s of 1.3 and 15.8 nM, about 241-and 149-fold more 45 potent than that of EK1 peptide, respectively.
| |
| it | study | fusion capacity of SARS-CoV-2 (count: 1) | |
| To develop specific SARS-CoV-2 80 fusion inhibitors, it is essential to study the fusion capacity of SARS-CoV-2 compared 81 to that of SARS-CoV. Particularly, the spike (S) protein S2 subunit of SARS-CoV-2, We have solved the X-ray crystal structure of SARS-CoV-2's 6-HB core and 111 identified several mutated amino acid residues in HR1 domain responsible for its 112 enhanced interactions with HR2 domain.
| |
| we | located | domains in SARS-CoV-2 S protein (count: 1) | |
| Through alignment with SARS-CoV and SL-CoVs S 127 proteins, we located the functional domains in SARS-CoV-2 S protein, which 128 contains S1 subunit and S2 subunit with the cleavage site at R685/S686 15 .
| |
| SARS-CoV-2 S protein | binds | hACE2 (count: 1) | |
| Recent biophysical and structural evidence showed that SARS-CoV-2 S protein 134 binds hACE2 with 10-fold to 20-fold higher affinity than SARS-CoV S protein, 135 suggesting the higher infectivity of the new virus 12 .
| |
| SARS-CoV-2 | mediate membrane fusion in | manner (count: 1) | |
| 85 Most importantly, the ACE2-binding affinity of the receptor-binding domain (RBD) in 86 S1 subunit of S protein of SARS-CoV-2 is 10-to 20-fold higher than that of 87 SARS-CoV 12 , which may contribute to the higher infectivity and transmissibility of 88 SARS-CoV-2 compared to SARS-CoV. However, it is unclear whether SARS-CoV-2 89 can mediate membrane fusion in a manner that exceeds the capacity of SARS-CoV. 90 After binding of RBD in S1 subunit of S protein on the virion to the ACE2 91 receptor on the target cell, the heptad repeat 1 (HR1) and 2 (HR2) domains in its S2 92 subunit of S protein interact with each other to form a six-helix bundle (6-HB) fusion 93 core, bringing viral and cellular membranes into close proximity for fusion and 94 infection 13 .
| |
| SARS-CoV-2 | exhibits | capacity of 108 membrane fusion than SARS-CoV (count: 1) | |
| 98 In our previous studies, we designed a pan-coronavirus fusion inhibitor, EK1, 99 targeting the HR1 domains of HCoV S proteins, which proved to be effective in In this study, we have shown that SARS-CoV-2 exhibits much higher capacity of 108 membrane fusion than SARS-CoV, suggesting that the fusion machinery of SARS-CoV-2 infection, we found a typical syncytium phenomenon naturally formed 139 by infected cells, which is rarely reported in SARS-CoV infection (Fig.
| |
| EK1C4 | is | SARS-CoV-2 fusion inhibitor (count: 1) | |
| Therefore, the selectivity index (SI=CC 50 /IC 50 ) of EK1C4 is >136, suggesting 307 that EK1C4 is a promising SARS-CoV-2 fusion inhibitor with little, or even no, toxic 308 effect in vitro.
| |
| RBD | is in | S protein of SARS-CoV-2 (count: 1) | |
| A recent study also found that the binding affinity 397 between ACE2 receptor on the host cell and RBD in S protein of SARS-CoV-2 is 398 more than 10-fold higher than that of SARS-CoV, which may also be associated with 399 the increased infectivity and transmissibility of SARS-CoV-2 12 .
| |
| SARS-CoV-2 S protein | mediating | entry (count: 1) | |
| Therefore, compared to SARS-CoV, SARS-CoV-2 S 158 protein showed much more efficiency in mediating viral surface-fusion and entry into 159 target cells 14 .
| |
| HR1 | is in | S2 subunit of SARS-CoV-2 S protein 165 (count: 1) | |
| -ray crystallographic analysis of the 6-HB fusion core formed by HR1 and HR2 164 domains in S2 subunit of SARS-CoV-2 S protein 165
| |
| them | could inhibit | SARS-CoV-2 233 fusion at concentration (count: 1) | |
| Both of them could completely inhibit SARS-CoV-2 mediated 233 cell-cell fusion at the concentration of 2.5 μM (Fig.
| |
| SARS-CoV-2 S protein | could mediate | formation (count: 1) | |
| Consistently, in the cell-cell 361 fusion system, SARS-CoV-2 S protein could effectively mediate the formation of 362 syncytium between the effector cell and the target cell in the absence of an exogenous 363 proteolytic enzyme, e.g., trypsin, while SARS-CoV S protein could not.
| |
| target cells 542 | 293T/ACE2 for | SARS-CoV-2 (count: 1) | |
| To 541 detect the inhibitory activity of a peptide on infection of coronavirus PsV, target cells 542 (293T/ACE2 for SARS-CoV-2, SARS-CoV and SL-CoVs; RD cells for HCoV-OC43; 543 Huh-7 for other CoVs) were plated at a density of 10 4 cells per well in a 96-well plate 544 one day prior to infection 14 .
| |
| sequence | investigate | potential codon usage of spike protein from SARS-CoV-2 (count: 1) | |
| To investigate the potential relative synonymous codon usage (RSCU) bias of the spike protein from SARS-CoV-2 and its closely related coronaviruses, the coding sequence (CDS) of spike protein in these coronaviruses were calculated with CodonW 1.4.4 (http://codonw.sourceforge.net/).
| |
| SARS-CoV-2 virions | bind via | interactions (count: 1) | |
| SARS-CoV-2 virions bind to the ACE2 receptor on the surface of cells via interactions with the Spike protein.
-- Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza. biorxiv. 2020-03-14. | |
| S protein | including SARS-CoV-2 is | six 24 proteins (count: 1) | |
| By investigating the entire proteome of SARS-CoV-2, six 24 proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), 25 were predicted to be adhesins, which are crucial to the viral adhering and host invasion.
-- reference not found! | |
| S protein | was predicted In | SARS-CoV-2 (count: 1) | |
| In SARS-CoV-2, S protein was predicted to be adhesin, 151 matching its primary role in virus entry.
-- reference not found! | |
| 2019-nCoV S protein | engages | ACE2 (count: 1) | |
| SARS-CoV S protein and 2019-nCoV S protein engages angiotensin-converting enzyme 2 (ACE2) as their entry receptor (Li et al.,
| |
| ACE2 level | is factor for | 2019-nCoV infection (count: 1) | |
| The ACE2 level is the decisive factor for 2019-nCoV infection .
| |
| approach | identify | potential T-cell epitopes based on S protein of SARS-CoV-2 (count: 1) | |
| In this manuscript, we applied immuno-informatics approach to identify potential B-and T-cell epitopes based on the S protein of SARS-CoV-2.
-- Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2. biorxiv. 2020-02-27. | |
| Location | predicted | DiscoTope 2 on 3D structure of SARS-CoV-2 S protein (count: 1) | |
| Location of discontinuous B-cell epitopes predicted throough DiscoTope 2 on the 3D structure of the SARS-CoV-2 S protein (PDB ID 6VSB).
-- Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2. biorxiv. 2020-02-27. | |
| tree | show | relationship of SARS-CoV-2 S protein (count: 1) | |
| A phylogenetic tree was generated to show the evolutionary relationship of SARS-CoV-2 S protein collected from 38 locations worldwide (Figure 5).
-- Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2. biorxiv. 2020-02-27. | |
| CD147 | spike protein of | SARS-CoV-2 (count: 1) | |
| It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion.
-- reference not found! | |
| current published data | showed | interaction between spike protein of SARS-CoV-2 (count: 1) | |
| 12 Our current published data showed a direct interaction between spike protein of SARS-CoV-2 and CD147, a type I transmembrane glycoprotein expressed on epithelial cells.
-- reference not found! | |
| 2019-nCoV | use pig ACE2 as | entry receptor (count: 1) | |
| had experimentally confirmed that 2019-nCoV is able to use human, Chinese 18 horseshoe bats, civet, and pig ACE2 as an entry receptor in the ACE2-expressing cells(2), 19 suggesting the RBD of 2019-nCoV mediates infection to human and other animals.
-- Pangolin homology associated with 2019-nCoV. biorxiv. 2020-02-20. | |
| fusion proteins | neutralized | 2019-nCoV (count: 1) | |
| Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro.
-- Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig. biorxiv. 2020-02-03. | |
| 2019-nCoV | may use proteins as | ACE2 partner (count: 1) | |
| 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry.
| |
| 2019-nCoV-S | uses ACE2 for | entry (count: 1) | |
| recently showed that 2019-nCoV-S uses ACE2 for entry and depends on the cellular protease TMPRSS2 for priming [10] , showing that 2019-nCoV infections also require multiple factors.
| |
| 2019-nCoV | bind on | surface (count: 1) | |
| It was found that 2019-nCoV was able to bind to ACE2 receptor on the surface of epithelial cells.
-- Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV. medrxiv. 2020-02-05. | |
| 2019-nCoV | have | ACE2 receptor (count: 1) | |
| calculated and simulated that 2019-nCoV may have the same ACE2 receptor as SARS, although its binding ability to ACE2 was weaker than SARS.
-- Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV. medrxiv. 2020-02-05. | |
| virion protein | is | During 2019-nCoV 's infection Spike surface glycoprotein known as S protein (count: 1) | |
| During the 2019-nCoV's infection of host cells, a critical virion protein is the Spike surface glycoprotein, also known as the S protein.
| |
| entitled Uncanny similarity | is in | 2019-nCoV spike protein to HIV-1 gp120 (count: 1) | |
| In a recent manuscript entitled "Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag" 3 , Pradhan et al.
| |
| SARS-CoV-2 | enters body through | ACE2 receptors (count: 1) | |
| Researchers have confirmed that SARS-CoV-2 enters the human body through ACE2 receptors on the surface of human cells and causes disease 5 .
-- reference not found! | |
| SARS-CoV-2 | enter body through | ACE2 receptors (count: 1) | |
| Moreover, recent study showed that SARS-CoV-2 could enter the human body through ACE2 receptors on the surface of human cells and causes disease 5 .
-- reference not found! | |
| 10 | reported structure at | 3.5 Å resolution of SARS-CoV-2 S protein (count: 1) | |
| 10] reported a structure at 3.5 Å resolution of SARS-CoV-2 S protein.
-- Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM. biorxiv. 2020-03-05. | |
| 11 | reported | structure of SARS-CoV-2 S protein (count: 1) | |
| 11] reported the complex structure of SARS-CoV-2 S protein with human host cell binding receptor angiotensin-converting enzyme 2 (ACE2).
-- Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM. biorxiv. 2020-03-05. | |
| SARS-CoV-2 S protein | 's domain is | RBD (count: 1) | |
| 12] reported crystal structure of SARS-CoV-2 S protein's receptor binding domain (RBD) region binding with ACE2.
-- Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM. biorxiv. 2020-03-05. | |
| SARS-CoV-2 | bind to | receptor (count: 1) | |
| SARS-CoV-2 seems to bind to the same receptor to infect target cells 21 .
-- Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. medrxiv. 2020-03-16. | |
| ACE2 peptidase domain α1 helix | is | 38 important for SARS-CoV-2-RBD (count: 1) | |
| CoV-2-RBD co-crystal structure, we observed that the ACE2 peptidase domain (PD) α1 helix is 38 important for binding SARS-CoV-2-RBD.
-- reference not found! | |
| viral SARS-CoV-2-RBD-host ACE2 interaction | is with | 72 peptide-based binders (count: 1) | |
| We hypothesize that disruption of the viral SARS-CoV-2-RBD-host ACE2 interaction with 72 peptide-based binders will prevent virus entry into human cells, offering a novel opportunity for 73 therapeutic intervention.
-- reference not found! | |
| 143 | use peptide as | point for development of 144 SARS-CoV-2 spike protein binder (count: 1) | |
| We 143 decided to use this peptide (SBP1) as an experimental starting point for the development of a 144 SARS-CoV-2 spike protein binder.
-- reference not found! | |
| binding affinity | is comparable with | that of length ACE2 binding to SARS-CoV-2-RBD 152 (count: 1) | |
| This binding affinity is comparable with that of full length ACE2 binding to SARS-CoV-2-RBD 152 (14.7 nM) [7] .
-- reference not found! | |
| peptide sequence | bind | 162 SARS-CoV-2 spike protein RBD (count: 1) | |
| In conclusion, a peptide sequence derived from human ACE2 was found to bind the 162 SARS-CoV-2 spike protein RBD with low nanomolar affinity.
-- reference not found! | |
| CoV-2-RBD ACE2 binding interface | paves | way for COVID-19 treatment (count: 1) | |
| CoV-2-RBD/ACE2 binding interface with high-affinity peptides represents a promising strategy for 164 preventing virus entry in human cells and paves the way for new COVID-19 treatment and 165 diagnostic modalities.
-- reference not found! | |
| binding simulations | point of was | cryo-electron microscopy model of SARS-CoV-2 spike 134 protein derived from binding domain of ACE2 135 protein (count: 1) | |
| The starting 133 point of the binding simulations was the cryo-electron microscopy model of SARS-CoV-2 spike 134 protein and several peptides derived from the SARS-CoV-2-spike binding domain of human ACE2 135 protein.
-- reference not found! | |
| ACE2 receptor | may | may component for 2019-nCoV infect (count: 1) | |
| Therefore ACE2 receptor may be the key component for 2019-nCoV to infect human and transmit in the host body.
| |
| 2019-nCoV | interact with | ACE2 receptor (count: 1) | |
| Therefore, we speculates that 2019-nCoV may interact with ACE2 receptor in gastrointestinal tract, then further impair the intestinal mucous membrane barrier and increase the inflammatory cytokines production.
| |
| two major differences | is in | RBD region of SARS-CoV-2 S protein 32 (count: 1) | |
| The 31 sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein 32 compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV).
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| β-sheet structure | deleted in | SARS-CoV-2 S protein (count: 1) | |
| Epitope analysis of neutralizing antibodies revealed that 34 SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies 35 used a common linear epitope region, which contributes to form the β-sheet structure in MERS-CoV S protein 36 and deleted in SARS-CoV-2 S protein.
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| 39 | have | binding affinity with SARS-CoV-2 S protein (count: 1) | |
| The result showed that CR3022 neutralizing antibody from human may 39 have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein.
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| ACE2 | binds to | SARS-CoV-2 S protein (count: 1) | |
| McLaellen and colleges showed that ACE2 binds to SARS-CoV-2 S protein with much higher affinity than 76 to SARS-CoV S protein [15] .
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| C Intersertional regions | is in | SARS-CoV-2 391 S protein (count: 1) | |
| C) Intersertional regions in SARS-CoV-2 391 S protein.
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| sky color | represents | 407 SARS-CoV-2 S protein (count: 1) | |
| The sky blue color represents 407 SARS-CoV-2 S protein and the RBD domain were highlighted with orange color.
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| S protein | is in | SARS-CoV-2 (count: 1) | |
| The bootstrap values of the phylogenetic treeConservation score and epitope mapping of SARS-CoV-2 S proteinThe conservation score of amino acid positions on S protein in SARS-CoV-2 was calculated by ConSurf 105 program[27].
-- Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2. biorxiv. 2020-02-27. | |
| FBLN5 EFEMP2 LTBP4 CFTR G6PC3 PLG GRHL2 COL5A1 SERPINA1 COX4I2 MEFV MUSK RAPSN GBA HPS1 GLI2 CBS DOCK8 SARS2 FLG STIM1 CARD11 PGM3 TYK2 NFKB2 LRBA MARS ITGA3 SMAD4 MGP PTPN11 TGFBR1 DLEC1 DLC1 RASSF1 PPP2R1B KRAS MAP3K8 NSMCE3 TSC1 TSC2 FBN1 STRA6 RARB ZEB2 ACTA2 SPINK5 NF1 IRF1 PIK3CA SOS1 HGF RIT1 PPP1CB LEP GATA6 CDSN ARPC1B PLA2G7 FAM111B PEPD AKT1 SLC34A2 RTEL1 PARN SFTPA2 BMPR2 SMAD9 CAV1 KCNK3 EIF2AK4 IGFBP7 GDF1 CREBBP GPC3 RB1 MTOR DHCR7 ELN SFTPB SFTPC ABCA3 CSF2RA CSF2RB ENG ACVRL1 RSPO2 GATA4 NKX2 TBX1 ZFPM2 GTF2H5 SCARF2 | WAS | IL21R IL13 TERC CLEC7A IRAK3 PTGER2 ALOX5 ADRB2 MUC7 PTGDR NPSR1 HLA.G CCL11 HNMT SCGB3A2 TNF CHI3L1 IL4R MS4A2 COPA TGFB1 CAPN10 CHRNA3 CHRNA5 CASP8 CYP2A6 ERCC6 FASLG IRGM MC3R SLC11A1 CCL2 CD209 SP110 TLR2 DDX41 GLUD2 ATXN2 ADH1C MAPT TBP FCGR2A HMOX1 TERT MUC5B CPS1 IFNGR1 IFNG TIRAP CISH GSDMB GSDMA ZPBP2 HLA.DRB5 HLA.DQA1 RANBP6 IL33 SLC25A46 TSLP IL1RL2 IL1RL1 SMAD3 NOTCH4 PGAP3 MIEN1 IL18R1 HLA.DRB1 ORMDL3 HHIP HTR4 CLPTM1L CHRNB4 IRF4 MC1R SLC45A2 DEF8 RALY CHEK2 MUC5AC TOLLIP DSP TP63 ADAMTS7 MUC2 GSTCD CHRM3 AGER THSD4 HLA.DOA HSD17B8 RING1 COL11A2 RXRB HLA (count: 1) | |
| WDR19 DOK7 GGT1 WNT4 WNT3 PDE4D ARHGAP31 EGFR BRAF ERBB2 PRKN ADA NR0B1 JAG1 NOTCH2 ALMS1 FOXF1 TBX21 ITCH SDCCAG8 TTC8 AFF4 MMP1 CPN1 PLD1 MAP2K2 NKX2.1 TTF1 CCDC151 KRT18 KRT8 ALG9 ZIC3 HRAS FBLN5 EFEMP2 LTBP4 CFTR G6PC3 PLG GRHL2 COL5A1 SERPINA1 COX4I2 MEFV MUSK RAPSN GBA HPS1 GLI2 CBS DOCK8 SARS2 FLG STIM1 CARD11 PGM3 TYK2 NFKB2 LRBA MARS ITGA3 SMAD4 MGP PTPN11 TGFBR1 DLEC1 DLC1 RASSF1 PPP2R1B KRAS MAP3K8 NSMCE3 TSC1 TSC2 FBN1 STRA6 RARB ZEB2 ACTA2 SPINK5 NF1 IRF1 PIK3CA SOS1 HGF RIT1 PPP1CB LEP GATA6 CDSN ARPC1B PLA2G7 FAM111B PEPD AKT1 SLC34A2 RTEL1 PARN SFTPA2 BMPR2 SMAD9 CAV1 KCNK3 EIF2AK4 IGFBP7 GDF1 CREBBP GPC3 RB1 MTOR DHCR7 ELN SFTPB SFTPC ABCA3 CSF2RA CSF2RB ENG ACVRL1 RSPO2 GATA4 NKX2.5 TBX1 ZFPM2 GTF2H5 SCARF2 WAS IL21R IL13 TERC CLEC7A IRAK3 PTGER2 ALOX5 ADRB2 MUC7 PTGDR NPSR1 HLA.G CCL11 HNMT SCGB3A2 TNF CHI3L1 IL4R MS4A2 COPA TGFB1 CAPN10 CHRNA3 CHRNA5 CASP8 CYP2A6 ERCC6 FASLG IRGM MC3R SLC11A1 CCL2 CD209 SP110 TLR2 DDX41 GLUD2 ATXN2 ADH1C MAPT TBP FCGR2A HMOX1 TERT MUC5B CPS1 IFNGR1 IFNG TIRAP CISH GSDMB GSDMA ZPBP2 HLA.DRB5 HLA.DQA1 RANBP6 IL33 SLC25A46 TSLP IL1RL2 IL1RL1 SMAD3 NOTCH4 PGAP3 MIEN1 IL18R1 HLA.DRB1 ORMDL3 HHIP HTR4 CLPTM1L CHRNB4 IRF4 MC1R SLC45A2 DEF8 RALY CHEK2 MUC5AC TOLLIP DSP TP63 ADAMTS7 MUC2 GSTCD NPNT CHRM3 AGER THSD4 HLA.DOA HSD17B8 RING1 COL11A2 RXRB HLA.
-- reference not found! | |
| 2019-nCoV | use ACE2 as | receptor 20 (count: 1) | |
| 2019-nCoV has recently been confirmed to use the human ACE2 as receptor 20 .
-- Mutations, Recombination and Insertion in the Evolution of 2019-nCoV. biorxiv. 2020-03-02. | |
| studies | have indicated ACE2 as | entry receptor for 2019-nCoV 29 (count: 1) | |
| Recent studies have indicated ACE2 as the entry receptor for 2019-nCoV 29 although other host cell factors such as TMPRSS2 are likely involved 30 .
-- Mutations, Recombination and Insertion in the Evolution of 2019-nCoV. biorxiv. 2020-03-02. | |
| 2019-nCoV Spike | is in | Prefusion Conformation (count: 1) | |
| Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation.
-- Mutations, Recombination and Insertion in the Evolution of 2019-nCoV. biorxiv. 2020-03-02. | |
| 2019-nCoV | bind to | ACE2 (count: 1) | |
| Our results show that the human receptor-binding affinity of 2019-nCoV is about 73% of that of SARS-CoV, implying that 2019-nCoV is able to bind to ACE2, and thereby infects the human host cells like SARS-CoV.
-- Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). biorxiv. 2020-02-04. | |
| model | was | used as 3D structure of 2019-nCoV S-RBD for docking with structure of ACE2 from PDB (count: 1) | |
| The top-1 scoring model was used as the 3D structure of the 2019-nCoV S-RBD for the protein-protein docking with the experimental structure of ACE2 from PDB .
-- Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). biorxiv. 2020-02-04. | |
| we | obtained | configuration of S-RBD complexed with ACE2 for 2019-nCoV docking (count: 1) | |
| 2B) , we obtained the starting configuration of S-RBD complexed with ACE2 for the 2019-nCoV docking (Fig.
-- Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). biorxiv. 2020-02-04. | |
| 2019-nCoV | reaches | about 73 % of ACE2 strength (count: 1) | |
| We have performed large-scale protein-protein docking to evaluate the binding affinities of SARS-CoV and 2019-nCoV S-RBDs to the human receptor ACE2, in order to quantitatively assess the human receptor-binding capability of 2019-nCoV. Using the well-investigated SARS-CoV as the reference, our results showed that 2019-nCoV reaches about 73% of the ACE2 receptor-binding strength of SARS-CoV. This supports that the 2019-nCoV S-protein encoded by its genome has processed human receptor-binding ability close to that of SARS-CoV, and thus this newly emerged virus is likely able to bind to ACE2 and then to drive human-to-human transmission.
-- Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). biorxiv. 2020-02-04. | |
| results | viral titers of | 2019-nCoV (count: 1) | |
| Combining the results of ACE2-expressing cells in the nasal brushing and turbinate samples and the viral titers of 2019-nCoV in patients' nasal-and throat-swabs, we infer that there exists a significant number of 2019-nCoV host cells in the nasal tissue.
| |
| 2019-nCoV-S | employs | ACE2 74 (count: 1) | |
| However, it is unknown whether 2019-nCoV-S like SARS-S employs ACE2 74 and TMPRSS2 for host cell entry.
| |
| 2019-nCoV-S | utilizes ACE2 as | receptor (count: 1) | |
| 2019-nCoV-S utilizes ACE2 as cellular receptor. (
| |
| 2019-nCoV | possesses | amino acid residues crucial for 302 ACE2 binding (count: 1) | |
| B) Alignment of the receptor binding motif of SARS-S with 300 corresponding sequences of bat-associated betacoronavirus S proteins that are able or unable to 301 use ACE2 as cellular receptor reveals that 2019-nCoV possesses amino acid residues crucial for 302 ACE2 binding. (
| |
| 2019-nCoV | possesses | amino acid residues crucial for 348 ACE2 binding (count: 1) | |
| B) Alignment of the receptor binding motif of SARS-S with 346 corresponding sequences of bat-associated betacoronavirus S proteins that are able or unable to 347 use ACE2 as cellular receptor reveals that 2019-nCoV possesses amino acid residues crucial for 348 ACE2 binding. (
| |
| 2019-nCoV-S | employs TMPRSS2 for | S protein priming (count: 1) | |
| 2019-nCoV-S employs TMPRSS2 for S protein priming.
| |
| agreement | is with | separate studies on diffusion of 2019-nCoV virus in China (count: 1) | |
| This is in agreement with separate studies on the diffusion of the 2019-nCoV virus in China (29; 21; 30).
-- The effect of travel restrictions on the spread of the 2019 novel coronavirus (2019-nCoV) outbreak. medrxiv. 2020-02-11. | |
| SARS-CoV-2 | infect cells through | interaction of S proteins (count: 1) | |
| SARS-CoV and SARS-CoV-2 have been shown to infect human respiratory epithelial cells through the interaction of viral S proteins and angiotensin-converting enzyme 2 receptors on human cells[26, 49] .
-- reference not found! | |
| 2019-nCoV | bind through | changes (count: 1) | |
| The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes.
-- Predictions for the binding domain and potential new drug targets of 2019-nCoV. biorxiv. 2020-03-02. | |
| 2019-nCoV | have | ACE2 binding model (count: 1) | |
| Therefore, we speculated that 2019-nCoV and SARS may have the same ACE2 binding model.
-- Predictions for the binding domain and potential new drug targets of 2019-nCoV. biorxiv. 2020-03-02. | |
| 2019-nCoV | spike protein of be | should trimer (count: 1) | |
| Previous reports have suggested that the conformational transformation of CTD1 from bottom to top was a prerequisite for receptor binding 13 , and that the spike protein of 2019-nCoV should also be trimer.
-- Predictions for the binding domain and potential new drug targets of 2019-nCoV. biorxiv. 2020-03-02. | |
| 4 mAbs | bound to | 1 7 8 S protein of SARS-CoV-2 (count: 1) | |
| As shown in Figure 3 , all 4 mAbs bound to the full-length 1 7 8 S protein of SARS-CoV-2.
| |
| deterioration | diffusion of | epidemic of COVID-19 (count: 1) | |
| To control the diffusion and deterioration of the epidemic of COVID-19 in China, the Chinese government implemented series of strict and unprecedented intervention strategies [5, 6] .
| |
| Wuhan | limit | diffusion of patients with COVID-19 (count: 1) | |
| For example, on January 21, 2020, COVID-19 was classed as a Class B infectious disease and was controlled as a Class A infectious disease; on January 23, 2020, Wuhan was quarantined to limit the diffusion of patients with COVID-19.
| |
| medRxiv | diffusion of | COVID-19 (count: 1) | |
| https://doi.org/10.1101/2020.03.10.20032755 doi: medRxiv preprint the diffusion and deterioration of COVID-19 in mainland China, we implemented model fitting and designed an index named Speedmax, which represented the time when the growth speed of the cumulative confirmed cases reached its maximum.
| |
| countries | diffusion of | COVID-19 (count: 1) | |
| These strategies therefore provide experience and effective guidelines for other countries to control the diffusion of COVID-19.
| |
| SARS-CoV-2 | use ACE2 as | their receptors (count: 1) | |
| Although both SARS-CoV and SARS-CoV-2 use the human ACE2 as their receptors (8, 20) they show a high level of genetic divergence (figs.
-- reference not found! | |
| SARS-CoV-2 | is in | context of type I IFN 10 (count: 1) | |
| Examining transcriptional factor activation 9 and interferon stimulated gene (ISG) induction, SARS-CoV-2 in the context of type I IFN 10 induces phosphorylation of STAT1 and increased ISG proteins.
-- reference not found! | |
| SARS-CoV-2 | modulates | type I IFN response (count: 1) | |
| as well as further research into how SARS-CoV-2 modulates the type I IFN response early 23 during infection.
-- reference not found! | |
| several vaccine efforts | have | have initiated with focus on SARS-CoV-2 spike protein as 50 determinate 13 (count: 1) | |
| Importantly, several vaccine efforts 49 have been initiated with a focus on the SARS-CoV-2 spike protein as the major antigenic 50 determinate 13 .
-- reference not found! | |
| We | evaluated | susceptibility of SARS-CoV-2 to IFN-I pretreatment (count: 1) | |
| We next evaluated the susceptibility of SARS-CoV-2 to IFN-I pretreatment.
-- reference not found! | |
| we | examined protein production in | 96 nucleocapsid protein production in IFN-I cells following SARS-CoV-2 infection (count: 1) | |
| Finally, we examined viral protein production finding a major deficit in 96 nucleocapsid protein production in IFN-I treated cells following SARS-CoV-2 infection (Fig.
-- reference not found! | |
| primed 99 IFN-I response | is in | SARS-CoV-2 (count: 1) | |
| Together, the results demonstrate a clear sensitivity to a primed 99 IFN-I response in SARS-CoV-2, which is not observed with SARS-CoV. 100 SARS-CoV-2 fails to attenuate STAT1 phosphorylation and ISG production.
-- reference not found! | |
| IFN-I cells | infected with | SARS-CoV-2 (count: 1) | |
| Examining Vero cell protein lysates, we found that IFN-I treated cells infected with 104 SARS-CoV-2 induced phosphorylated STAT-1 by 48 hours post infection (Fig.
-- reference not found! | |
| IFN-I treatment | results in | protein levels for 113 ISGs following SARS-CoV-2 infection (count: 1) | |
| However, IFN-I treatment results in augmented protein levels for 113 both ISGs following SARS-CoV-2 infection as compared to untreated control.
-- reference not found! | |
| differences | be | 147 drivers of SARS-CoV-2 type I IFN susceptibility (count: 1) | |
| Together, the 146 sequence homology analysis suggests that differences in NSP3, ORF3b, and/or ORF6 may be 147 key drivers of SARS-CoV-2 type I IFN susceptibility.
-- reference not found! | |
| differences | is in | 151 IFN-I sensitivity between SARS-CoV-2 (count: 1) | |
| In this report, we describe differences in 151 the IFN-I sensitivity between SARS-CoV-2 and the original SARS-CoV. While both viruses 152 maintain similar replication in untreated Vero E6 cells, SARS-CoV-2 has a significant decrease 153 in viral protein and replication following IFN-I pretreatment.
-- reference not found! | |
| SARS-CoV-2 | has | changes known as IFN-I antagonists (count: 1) | |
| Analysis of viral proteins finds SARS-CoV-2 has several changes that potentially impact its 158 capacity to modulate the type I IFN response, including loss of ORF3b and a short truncation of 159 ORF6, both known as IFN-I antagonists for SARS-CoV 30 .
-- reference not found! | |
| SARS-CoV-2 | sensitivity to | type I IFN 230 (count: 1) | |
| Overall, our results indicate that SARS-CoV-2 has a much higher sensitivity to type I IFN 230 than the previously emergent SARS-CoV. This augmented type I IFN sensitivity is likely due to 231 changes in viral proteins between the two epidemic CoV strains.
-- reference not found! | |
| SARS-CoV-2 | shows | 93 reduction following IFN-I treatment (count: 1) | |
| In contrast, SARS-CoV-2 shows a significant 93 reduction in viral replication following IFN-I treatment.
-- reference not found! | |
| STAT1 phosphorylation | is | following IFN-I pretreatment induced following SARS-CoV-2 infection (count: 1) | |
| In these studies, we have found that following IFN-I pretreatment, STAT1 191 phosphorylation is induced following SARS-CoV-2 infection.
-- reference not found! | |
| wS protein | is in | 2019-nCoV (count: 1) | |
| Similar to SARS-CoV [66] , wS protein in 2019-nCoV is expected to interact with type II transmembrane protease (TMPRSS2) [67] and is likely to be involved in inhibition of antibody-mediated neutralization.
| |
| We | modeled | interactions between 2019-nCoV wS protein (count: 1) | |
| We also structurally modeled interactions between the 2019-nCoV wS protein and three human .
| |
| SARS-CoV antibody | bind to | SARS-CoV-2 RBD (count: 1) | |
| Early reports, have described that the human SARS-CoV antibody, CR3022, is able to bind to the SARS-CoV-2 RBD.
-- A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein. biorxiv. 2020-03-17. | |
| Structure comparison | is with | stabilized prefusion SARS-CoV-2 Spike (count: 1) | |
| Structure comparison of the unliganded RBD structure presented here, with the stabilized prefusion SARS-CoV-2 Spike (S-2P) molecule structure determined by Cryo-EM (PDB ID: 6VSB) (Wrapp et al.,
-- A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein. biorxiv. 2020-03-17. | |
| E SARS-CoV-2 RBD | was bound by | antibodies followed by ACE2 receptor (count: 1) | |
| E SARS-CoV-2 RBD was sequentially bound by antibodies CR3022 or 240CD followed by soluble human ACE2 receptor.
-- A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein. biorxiv. 2020-03-17. | |
| Pseudovirus | expressing | SARS-CoV-2 S protein (count: 1) | |
| Pseudovirus expressing the SARS-CoV-2 S protein was produced as described previously 19 .
-- reference not found! | |
| 2019-nCoV | uses ACE2 as | 9 (count: 1) | |
| Computational modeling analyses suggested that, similar to SARS-CoV, the 2019-nCoV uses ACE2 as the receptor [9] .
-- Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ?. biorxiv. 2020-02-20. | |
| Graphs | represent | disorder propensity of residue in S protein of SARS-CoV-2 (count: 1) | |
| Graphs in figures 3A, 3B and 3C represent the intrinsic disorder propensity of each residue in S protein of SARS-CoV-2, Human SARS and Bat CoV obtained from six disorder predictors.
-- Dark proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses. biorxiv. 2020-03-14. | |
| 2019-nCoV | utilizes cell entry receptor ACE2 as | SARS-CoV (count: 1) | |
| As 2019-nCoV utilizes the same cell entry receptor ACE2 as severe acute respiratory syndrome coronavirus (SARS-CoV) and ACE2 tightly controls intestinal inflammation, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis.
-- Diarrhea may be underestimated: a missing link in 2019 novel coronavirus. medrxiv. 2020-02-11. | |
| 2019-nCoV | shared entry receptor ACE2 as | SARS-CoV 7 (count: 1) | |
| Phylogenetic analysis of the viral genome indicates that the genome organization of this novel coronavirus is most closely related to that of the bat SARS-CoV. Interestingly, subsequent results showed that 2019-nCoV shared the same cellular entry receptor ACE2 as SARS-CoV 7 .
-- Diarrhea may be underestimated: a missing link in 2019 novel coronavirus. medrxiv. 2020-02-11. | |
| ACE2 mRNA | is providing | prerequisite for 95 SARS-CoV-2 infection (count: 1) | |
| ACE2 mRNA is 94 highly expressed in gastrointestinal system 4 , providing a prerequisite for 95 SARS-CoV-2 infection.
-- Evidence for gastrointestinal infection of SARS-CoV-2. medrxiv. 2020-02-20. | |
| line | confirming | 163 importance of ACE2 protein expression for SARS-CoV-2 infection (count: 1) | |
| The data of 162 viral protein staining are in line with the data of ACE2 staining, confirming the 163 importance of ACE2 protein expression for SARS-CoV-2 infection.
-- Evidence for gastrointestinal infection of SARS-CoV-2. medrxiv. 2020-02-20. | |
| 2019-nCoV S trimer | is in | prefusion conformation (count: 1) | |
| To facilitate 4 medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM 5 structure of the 2019-nCoV S trimer in the prefusion conformation.
-- Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. biorxiv. 2020-02-15. | |
| therapeutic design efforts | using | 2019-nCoV S proteins (count: 1) | |
| Despite the relatively high degree of structural homology suggests that SARS-directed mAbs will not necessarily be cross-reactive and that future antibody 115 isolation and therapeutic design efforts will benefit from using 2019-nCoV S proteins as probes.
-- Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. biorxiv. 2020-02-15. | |
| ACE2 | is positioned above | 2019-nCoV S protein (count: 1) | |
| Averages have been rotated so that ACE2 is positioned above the 2019-nCoV S protein with respect to the viral membrane.
-- Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. biorxiv. 2020-02-15. | |
| cartoon | depicting | 2019-nCoV S protein (count: 1) | |
| A cartoon depicting the ACE2-bound 2019-nCoV S protein is shown (right) with ACE2 in blue and S protein monomers colored tan, pink and green.
-- Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. biorxiv. 2020-02-15. | |
| 2019-nCoV S | binds ACE2 with | affinity (count: 1) | |
| 2019-nCoV S binds human ACE2 with high affinity. (
-- Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. biorxiv. 2020-02-15. | |
| cells | expressing | spike protein of SARS-CoV-2 (count: 1) | |
| Seroconversion was detected by IgG and IgM immunofluorescence using cells expressing the spike protein of SARS-CoV-2 and a virus neutralization assay using SARS-CoV-2 ( Table 3 ).
| |
| SARS-CoV-2 | undergoes membrane fusion | binding to ACE2 via its protein (count: 1) | |
| After binding to ACE2 via its Spike protein, SARS-CoV-2 undergoes membrane fusion and enters the host cells by endocytosis.
| |
| COVID-19 patients | is in | ChongqingIFN-γ ≥ 7.42 (count: 1) | |
| Laboratory and radiographic and findings of COVID-19 patients in ChongqingIFN-γ≥7.42 ng/ml -No./total No. (%)
| |
| examination | shows | proportion of amino acid sites in receptor binding domain of spike protein between COVID-19 (count: 1) | |
| Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences.
| |
| 97.43 % spike protein similarity | is with | SARS-CoV-2 (count: 1) | |
| Furthermore, RaTG13 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTG13 is the closest strain.
-- reference not found! | |
| We | constructed | model for complex formed between ACE2 of 14 2019-nCoV S-protein (count: 1) | |
| We 13 further constructed a structural model for complex formed between ACE2 and RBD of 14 2019-nCoV S-protein, so that the rate of their association can be estimated by a coarse-15 grained Monte-Carlo simulation and further compared with the binding of S-protein from 16 SARS-CoV. Our simulation indicates that association of the new virus to the receptor is 17 slower than SARS, which is consistent with the experimental data obtained very recently.
| |
| RBD | is in | S protein of 2019-nCoV (count: 1) | |
| These data indicate that the RBD in S protein of 2019-nCoV may bind to ACE2 with a similar affinity as SARS-CoV RBD does.
-- reference not found! | |
| we | measured | binding of 2019-nCoV RBD to ACE2 by biolayer interferometry binding (count: 1) | |
| Indeed, we measured the binding of 2019-nCoV RBD to human ACE2 by the biolayer interferometry binding (BLI) assay, and found that 2019-nCoV RBD bound potently to ACE2.
-- reference not found! | |
| Numbers | refer to | SARS-CoV-2 spike protein sequence (count: 1) | |
| Numbers refer to the SARS-CoV-2 spike protein sequence.
-- reference not found! | |
| 2019-nCoV | uses | ACE2 receptors (count: 1) | |
| In addition, another rapid report links demonstrates 2019-nCoV uses ACE2 receptors from human, bat, civets, and swine [30] .
-- Return of the Coronavirus: 2019-nCoV. Viruses. 2020. | |
| we | understand | possible relationship of 2019-nCoV S protein (count: 1) | |
| To better understand the possible relationship of the 2019-nCoV S protein to other coronaviruses, we generated a phylogenetic tree of S protein sequences from various human and animal coronaviruses (Figure 2 ).
-- 2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness. Journal of Infection in Developing Countries. 2020. | |
| 2019-nCoV S | resembles | S protein (count: 1) | |
| Our phylogenetic data shows that 2019-nCoV S most closely resembles the S protein from a SARS-like bat CoV followed by SARS-CoV and distantly resembles other human coronaviruses including the MERS-CoV S protein.
-- 2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness. Journal of Infection in Developing Countries. 2020. | |
| ACE2 molecules | has | potential interact with RBD of 2019-nCoV (count: 1) | |
| ACE2 molecules from any of these has the potential to interact with RBD of 2019-nCoV with high affinity.
-- reference not found! | |
| 2019-nCoV | Considering | expression of ACE2 in intestines (count: 1) | |
| Considering the predominant expression of ACE2 in intestines and kidney, 2019-nCoV may infect cells in these tissues and find its way into feces and urine.
-- reference not found! | |
| 2019-nCoV/SARS-CoV | utilize ACE2 as | entry receptor (count: 1) | |
| A recent study showed that 2019-nCoV/SARS-CoV-2 is able to utilize ACE2 as an entry receptor in ACE2-expressing cells 33 , suggesting potential drug targets for therapeutic development.
-- reference not found! | |
| Difference | is in | spike protein encoded by 2019-nCoV (count: 1) | |
| Difference in spike protein encoded by 2019-nCoV compared with the Bat SARS-like CoVs, SARS-CoV, and MERS-CoV is depicted in Figure 5 .
-- reference not found! | |
| insertions | is in | N-terminal domain of S protein of 2019-nCoV (count: 1) | |
| Whether the insertions in the N-terminal domain of the S protein of 2019-nCoV confer sialic-acid-binding activity as it does in MERS-CoV needs to be further studied.
| |
| 2019-nCoV | uses ACE2 as | entry receptor (count: 1) | |
| To determine whether 2019-nCoV also uses ACE2 as a cellular entry receptor, we conducted virus infectivity studies using HeLa cells that expressed or did not express ACE2 proteins from humans, Chinese horseshoe bats, civets, pigs and mice.
| |
| 2019-nCoV | use ACE2 proteins except for | mouse ACE2 (count: 1) | |
| We show that 2019-nCoV is able to use all ACE2 proteins, except for mouse ACE2, as an entry receptor to enter ACE2expressing cells, but not cells that did not express ACE2, indicating that ACE2 is probably the cell receptor through which 2019-nCoV enters cells (Fig.
| |
| mutation s | is in | sequence of spike protein of SARS-CoV-2 (count: 1) | |
| The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission.
-- reference not found! | |
| changes | have effect on | SARS-CoV-2 spike/ACE2 interaction (count: 1) | |
| The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor.
-- reference not found! | |
| loops | observed in | spike protein SARS-CoV-2 (count: 1) | |
| Thus, the loops observed in the spike protein of SARS-CoV-2 could play an important role together with the amino acid substitutions, being an interesting clue to determine the host receptor specificity for the viral spike protein.
-- reference not found! | |
| SARS-CoV-2 S protein | of epitopes is | 48 (count: 1) | |
| Further studies are currently under way to identify other SARS-CoV antibodies that may bind to discontinuous epitopes of the SARS-CoV-2 S protein [48] . (
| |
| 2019-nCoV | can bind to | ACE2 (count: 1) | |
| Although there are four amino acid variations of S protein between 2019-nCoV and SARS-CoV, 2019-nCoV can also bind to the human angiotensinconverting enzyme 2 (ACE2), the same host receptor for SARS-CoV, as 2019-nCoV can bind to the ACE2 receptor from the cells from human, bat, civet cat, and pig, but it cannot bind to the cells without ACE2 11, [33] [34] [35] .
-- Transmission routes of 2019-nCoV and controls in dental practice. International Journal of Oral Science. 2020. | |
| we | aligning | 2019-nCoV S protein sequence (count: 1) | |
| By aligning 2019-nCoV S protein sequence with those of SARS-CoV and several bat-SL-CoVs, we predicted that the cleavage site for generating S1 and S2 subunits is located at R694/S695 ( Figure 1 ).
-- An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020 Jan 31. | |
| representative scheme | is in | S protein of 2019-nCoV (count: 1) | |
| B) The representative scheme of functional domains in S protein of 2019-nCoV. SP, signal peptide; NTD, N-terminal domain; RBD, receptor-binding domain; FP, fusion peptide, HR1, heptad repeat 1; HR2, heptad repeat 2; TM, transmembrane domain; CP, cytoplasmic domain. (
-- An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020 Jan 31. | |
| ACE2 levels | would increase due to | SARS-CoV-2 infection (count: 1) | |
| Therefore, whether ACE2 levels would increase due to SARS-CoV-2 infection requires further investigation.
| |
| SARS-CoV-2 | uses ACE2 as | its entry point (count: 1) | |
| Recent evidence suggests SARS-CoV-2 uses ACE2 as its entry point; data that should speed the development of an effective drug and eventually a safe and effective vaccine.
-- reference not found! | |
| report | found | similarity in 2019-nCoV spike protein to HIV-1 gp120 (count: 1) | |
| A recent report found uncanny similarity of unique insertions in the 2019-nCoV spike protein to HIV-1 gp120 and Gag.
-- Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP). J Chin Med Assoc. 2020. | |
| remdesivir | could bind to | channel of SARS-CoV-2 RdRp (count: 1) | |
| Our molecular docking results show that the potential targets of remdesivir is Nsp3b (score=-36.5), RdRp (mfScores=-112.8), E-channel (mfScore=-125.1), and TMPRSS2 (score=-36.23, mfScores=-109.4).For RdRp, from generated docking model, remdesivir could bind to the RNA-binding channel of the SARS-CoV-2 RdRp, and the binding mode and site were highly similar to that of coxsackievirus B3 (CVB3)
-- reference not found! | |
| Bat-CoV RaTG13 protein | has | binding affinity with ACE2 compared to SARS-CoV-2 (count: 1) | |
| Unexpectedly, Bat-CoV RaTG13 Spike protein only has slightly weaker binding affinity with ACE2 compared to SARS-CoV-2.
-- reference not found! | |
| SARS-CoV-2 | uses ACE2 as | entry receptor (count: 1) | |
| 13] demonstrated that overexpressing ACE2 from different species in HeLa cells with human ACE2, pig ACE2, civet ACE2 (but not mouse ACE2) allowed SARS-CoV-2 infection and replication, thereby directly showing that SARS-CoV-2 uses ACE2 as a cellular entry receptor.
-- Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020. | |
| SARS-CoV-2 spike protein | binds with | host cell surface ACE2 receptor (count: 1) | |
| In summary, the SARS-CoV-2 spike protein directly binds with the host cell surface ACE2 receptor facilitating virus entry and replication.
-- Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020. | |
| spike protein priming | is essential for | entry of SARS-CoV-2 (count: 1) | |
| 25] recently demonstrated that initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is essential for entry and viral spread of SARS-CoV-2 through interaction with the ACE2 receptor [26, 27] .
-- Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020. | |
| ACE2 | bind with | SARS-CoV-2 (count: 1) | |
| This suggests that excessive ACE2 may competitively bind with SARS-CoV-2 not only to neutralize the virus but also rescue cellular ACE2 activity which negatively regulates the renin-angiotensin system (RAS) to protect the lung from injury [12, 30] .
-- Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020. | |
| SARS-CoV-2 | use | ACE2 receptor (count: 1) | |
| The finding that SARS-CoV-2 and SARS-CoV use the ACE2 receptor for cell entry has important implications for understanding SARS-CoV-2 transmissibility and pathogenesis.
-- Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020. | |
| Highlights d SARS-CoV-2 | uses SARS-CoV receptor ACE2 for | host cell entry d (count: 1) | |
| Highlights d SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry d The spike protein of SARS-CoV-2 is primed by TMPRSS2 d Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2
| |
| SARS-CoV-2 | possesses | amino acid residues for ACE2 binding (count: 1) | |
| B) Alignment of the receptor binding motif of SARS-S with corresponding sequences of bat-associated betacoronavirus S proteins, which are able or unable to use ACE2 as cellular receptor, reveals that SARS-CoV-2 possesses crucial amino acid residues for ACE2 binding.
| |
| SARS-CoV-2 | can use TMPRSS2 for | S protein (count: 1) | |
| Collectively, SARS-CoV-2 can use TMPRSS2 for S protein priming and camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells.
| |
| SARS-CoV-2 | interferes with | ACE2 expression (count: 1) | |
| It will thus be interesting to determine whether SARS-CoV-2 also interferes with ACE2 expression.
| |
| SARS-CoV-2 S proteins | have acquired | RRAR/S (count: 1) | |
| SARS-CoV-2 S proteins have also acquired several basic residues (RRAR/S), forming a furin protease cleavage site.
-- SARS Coronavirus Redux. Trends in Immunology. 2020-03-12. | |
| 2019-nCoV | bind to | enzyme 2 receptor (count: 1) | |
| Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensinconverting enzyme 2 receptor in humans.
| |
| 2019-nCoV | employ | ACE2 receptor (count: 1) | |
| Although a previous study using HeLa cells expressing ACE2 proteins showed that 2019-nCoV could employ the ACE2 receptor, 37 whether these mutations affect ACE2 binding or change receptor tropism requires further study.
| |
| difference | was | spike protein encoded by 2019-nCoV (count: 1) | |
| A notable difference was a longer spike protein encoded by 2019-nCoV compared with the bat SARS-like coronaviruses, SARS-CoV, and MERS-CoV (figure 1B).
| |
| amino acid sequence | is in | ACE2 receptor responsible for 2019-nCoV binding (count: 1) | |
| The amino acid sequence in the ACE2 receptor responsible for 2019-nCoV binding in farm animals and cats has only a few exchanges compared with the human receptor, suggesting that the species barrier for virus transmission is small.
-- reference not found! | |
| topology | is with | currently available spike protein gene sequences of 2019-nCoV (count: 1) | |
| The topology of a phylogenetic tree with all the currently available spike protein gene sequences of 2019-nCoV shows high similarities between human isolates ( Figure 2B ), indicating only minimal genetic variation, which is rather unexpected for fast evolving RNA viruses [42] .
-- reference not found! | |
| It | might | might desirable since their ACE2 receptor responsible for 2019-nCoV binding (count: 1) | |
| It might also be desirable to monitor farm animals and pet cats for infection with 2019-nCoV, since their ACE2 receptor responsible for 2019-nCoV binding differs in only a few amino acids from human ACE2.
-- reference not found! | |
| SARS-CoV-2 | utilise cell surface receptor ACE2 as | 85 86 (count: 1) | |
| Since SARS-CoV-2 was found a few days ago to utilise the same cell surface receptor ACE2 (expressed in lung, heart, kidney and intestine) as SARS-CoV-1 [85, 86] (Table 1) , it may be hypothesised that chloroquine also interferes with ACE2 receptor glycosylation thus preventing SARS-CoV-2 binding to target cells.
-- New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?. International Journal of Antimicrobial Agents. 2020-03-12. | |
| SARS-CoV-2 | may use proteins as | ACE2 partner (count: 1) | |
| SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry.
-- reference not found! | |
| SARS-CoV-2-S | uses ACE2 for | entry (count: 1) | |
| recently showed that SARS-CoV-2-S uses ACE2 for entry and depends on the cellular protease TMPRSS2 for priming [5] , showing that SARS-CoV-2 infections also require multiple factors.
-- reference not found! | |
| it | added | confusion concerning epidemiology of COVID-19 (count: 1) | |
| However, it also added more confusion concerning the epidemiology of COVID-19.
-- reference not found! | |
| SARS-CoV-2 entry | bind with | affinities (count: 1) | |
| Highlights d SARS-CoV-2 uses ACE2 to enter target cells d SARS-CoV-2 and SARS-CoV bind with similar affinities to ACE2 d Structures of SARS-CoV-2 spike glycoprotein in two conformations d SARS-CoV polyclonal antibodies inhibit SARS-CoV-2 spikemediated entry into cells
-- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020-03-09. | |
| SARS-CoV-2 S B | engages ACE2 with | affinity (count: 1) | |
| The SARS-CoV-2 S B engages human ACE2 (hACE2) with comparable affinity to SARS-CoV S B from viral isolates associated with the 2002-2003 epidemic (i.e., binding with high affinity to hACE2).
-- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020-03-09. | |
| SARS-CoV-2 S-MLV | use monkey ACE2 as | entry receptor (count: 1) | |
| Both pseudoviruses entered cells equally well ( Figure 1A ), suggesting that SARS-CoV-2 S-MLV could use African green monkey ACE2 as entry receptor.
-- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020-03-09. | |
| We | study | binding kinetics of hACE2 ectodomain to SARS-CoV-2 S B (count: 1) | |
| We used biolayer interferometry to study binding kinetics and affinity of the purified hACE2 ectodomain to SARS-CoV-2 S B and SARS-CoV S B immobilized at the surface of biosensors.
-- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020-03-09. | |
| SARS-CoV-2 S residues 473-486 | between hACE2 is | Data S1 (count: 1) | |
| However, we note that SARSr-CoV ZXC21 and ZC45, which harbor the most closely related S sequences after SARSr-CoV RaTG13, have a deletion in the RBD that could affect binding to hACE2 (between SARS-CoV-2 S residues 473-486 ) (Data S1).
-- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020-03-09. | |
| 2019-nCoV | use ACE2 as | cell entry receptor (count: 1) | |
| The spike gene of coronavirus has been shown to play a critical role in interspecies transmission: Zhou and colleagues found that 2019-nCoV can use ACE2 as a cell entry receptor.
-- Unveiling the Origin and Transmission of 2019-nCoV. Trends in Microbiology. 2020-04-30. | |
| He | was responsible of | diffusion of SARS-CoV-2 (count: 1) | |
| He was involuntarily responsible of the first diffusion of SARS-CoV-2 in Italy, considering his active social life and its hospitalization for "malaise" erroneously considered as simple influenza.
-- reference not found! | |
| SARS284 CoV-MA15 | formed | plaques in DBT-mACE2 cell monolayers (count: 1) | |
| In fact, SARS284 CoV-MA15 formed clear, easily identifiable plaques in DBT-mACE2 cell monolayers.
-- reference not found! | |
| potential CREs | is in | S protein of 2019-nCoV (count: 1) | |
| Further structural mapping showed the potential CREs in the S protein of 2019-nCoV (Fig.
-- Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus. Journal of Genetics and Genomics. 2020-01-30. | |
| we | examined | location for epitope region in S protein of 2019-nCoV (count: 1) | |
| In addition to the epitope similarity between 2019-nCoV and SARS-CoV, we also examined the location and residual distribution for each epitope region in S protein of 2019-nCoV. As Fig.
-- Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus. Journal of Genetics and Genomics. 2020-01-30. | |
| 2019-nCoV virus | is in | region of binding site of S proteins (count: 1) | |
| In summary, highly similar epitope was identified computationally between the 2019-nCoV and SARS virus, in the region of the binding site of the S proteins to the human ACE2 receptor.
-- Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus. Journal of Genetics and Genomics. 2020-01-30. | |
| Sites | are numbered based on | S protein sequence of 2019-nCoV (count: 1) | |
| Sites are numbered based on the S protein sequence of 2019-nCoV. Dot in the sequence of SARS-CoV represents gap insertion.
-- Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus. Journal of Genetics and Genomics. 2020-01-30. | |
| drugs | can bind to | RdRp of SARS-CoV-2 strain (count: 1) | |
| The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease.
-- reference not found! | |
| compounds | can bind to | SARS-CoV-2 RdRp (count: 1) | |
| Other compounds that are currently in clinical trials can bind to SARS-CoV-2 RdRp, with some showing promising results.
-- reference not found! | |
| SARS-CoV-2 | uses ACE2 In | fashion (count: 1) | |
| In similar fashion to SARS-CoV, SARS-CoV-2 also uses ACE2 to gain entry into host cells.
-- The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. Journal of Autoimmunity. 2020-03-03. | |
| SARS-CoV-2 | may bind via | expression (count: 1) | |
| SARS-CoV-2 may directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes via specific expression of ACE2 in healthy liver tissues using cell RNA-seq data of two independent cohorts [126] .
-- The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. Journal of Autoimmunity. 2020-03-03. | |
| SARS-CoV-2 | binds ACE2 with | above 10 (count: 1) | |
| A structure model analysis shows that SARS-CoV-2 binds ACE2 with above 10 folds higher affinity than SARS-CoV, but higher than the threshold required for virus infection [9] .
-- reference not found! | |
| 2019-nCoV | uses ACE2 as | 6 (count: 1) | |
| Second, when SARS broke out in 2003, angiotensin-converting enzyme 2 (ACE2) was confirmed to be a functional receptor for SARS-CoV. Interestingly, subsequent findings indicated that 2019-nCoV also uses ACE2 as an entry receptor [6] .
-- reference not found! | |
| study | In 21 is | spike protein of COVID-19 (count: 1) | |
| 21 In this study, the spike protein of COVID-19 was modeled using solved structures in the protein data bank.
-- reference not found! | |
| regions | are selected from | COVID-19 spike protein domain (count: 1) | |
| 28 Four regions are selected from the COVID-19 spike protein receptor-binding domain (RBD).
-- reference not found! | |
| SARS spike protein sequence | is closest to | COVID-19 spike (count: 1) | |
| The SARS spike protein sequence is the closest to the COVID-19 spike, with 77.38% identity.
-- reference not found! | |
| 39 interactions | formed between | spike protein COVID-19 (count: 1) | |
| 14 , 38 , 39 The interactions formed between the spike protein of COVID-19 and cell-surface GRP78 SBD β upon docking with HADDOCK.
-- reference not found! | |
| GRP78-COVID-19 spike protein docking | was | performed (count: 1) | |
| GRP78-COVID-19 spike protein docking was performed using the HADDOCK software in four different ways.
-- reference not found! | |
| hypothetical binding model | showing | homotrimer spike protein of COVID-19 (count: 1) | |
| 5 B shows a hypothetical binding model showing the homotrimer spike (red surface) protein of the COVID-19 bound to a respiratory system cell exposing the GRP78 protein (green surface).
-- reference not found! | |
| 13 disulfide bonds | is in | COVID-19 spike protein model (count: 1) | |
| We found 13 disulfide bonds in the COVID-19 spike protein model that form13 different cyclic regions that may resemble the cyclic Pep42.
-- reference not found! | |
| COVID-19 spike protein model | is in | colored cartoon representation (count: 1) | |
| shows the structure model of the COVID-19 spike protein model (homo-trimeric) in a colored cartoon representation.
-- reference not found! | |
| suggesting | risk of | transfusion transmission of SARS-CoV-2 (count: 1) | |
| The AABB, FDA, and Centers for Disease Control and Prevention do not currently require any action on blood collection and testing because there are no data suggesting a risk of transfusion transmission of SARS-CoV-2 [42] .
-- Coronavirus Disease 2019: Coronaviruses and Blood Safety. Transfusion Medicine Reviews. 2020-02-21. | |
| 2019-nCoV sequence | homology of was | 81 % with spike protein of Bat coronavirus (count: 1) | |
| As of 1/29/2020, the closest homology (sequence match) of the whole 2019-nCoV sequence (other than with its own entry at 100%) was 81% with the spike protein of the Bat SARS-like coronavirus, sequence ID GenBank entry AVP78031.1, with 100% coverage.
-- Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus. Computers in Biology and Medicine. 2020-02-26. | |
| 2019-nCoV uses | ACE2 as | its host receptor (count: 1) | |
| Structural analyses apparently predict that 2019-nCoV uses also the ACE2 as its host receptor ( Fig.
-- Going global – Travel and the 2019 novel coronavirus. Travel Medicine and Infectious Disease. 2020-02-29. | |
| N82 | contact with | SARS-CoV-2 S protein (count: 1) | |
| We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2.
-- reference not found! | |
| protein recognition | predicts | ACE2 for SARS-CoV-2 infection (count: 1) | |
| Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection, Biochemical and Biophysical Research Communications, https://doi.
-- reference not found! | |
| RBM | is in | S protein of SARS-CoV-2 (count: 1) | |
| We compared the RBM in S protein of SARS-CoV-2 with that of SARS-CoV (Fig.
-- reference not found! | |
| S protein | is in | RBD region of SARS-CoV-2 (count: 1) | |
| It shows that the transmission rate of SARS-CoV-2 is higher than SRAS-CoV and the reason could be genetic recombination event at S protein in the RBD region of SARS-CoV-2 may have enhanced its transmission ability.
-- COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research. 2020-03-16. | |
| SARS-CoV-2 | uses | ACE2 cell receptor (count: 1) | |
| In a fluorescent study, it was confirmed that the SARS-CoV-2 also uses the same ACE2 (angiotensin-converting enzyme 2) cell receptor and mechanism for the entry to host cell which is previously used by the SARS-CoV (39, 40) .
-- COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research. 2020-03-16. | |
| Clover Biopharmaceuticals | is developing | 2019-nCoV S protein subunit-trimer (count: 1) | |
| While Clover Biopharmaceuticals is developing a recombinant 2019-nCoV S protein subunit-trimer based vaccine (78).
-- COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research. 2020-03-16. | |
| It | find | effusion in patients with COVID-19 (count: 1) | |
| It is seldom to find pleural effusion in patients with COVID-19.
-- reference not found! | |
| BLAST comparison | is with | spike protein of SARS-CoV-2 (count: 1) | |
| A BLAST comparison with the spike protein of SARS-CoV-2 reveals 72.7% and 100% similarity respectively.
-- Is COVID-19 receiving ADE from other coronaviruses?. Microbes and Infection. 2020-03-31. | |
| limit | potential diffusion of | COVID-19 (count: 1) | |
| At the same time, rethinking our institutional radiotherapy (RT) fractionations by implementing hypofractionated schedules may represent, when feasible, the essential paradigm to decrease the access of cancer patients to the hospital and limit the potential diffusion of COVID-19.
-- reference not found! | |
| SARS-CoV-2 infection | leads to | downregulation of ACE2 expression (count: 1) | |
| SARS-CoV-2 infection leads to the downregulation of ACE2 expression, thus resulting in excessive production of angiotensin II by the related enzyme ACE.
-- reference not found! | |
| CR3022 | can bind with | domain of SARS-CoV-2 (count: 1) | |
| Moreover, the generation of recombinant human monoclonal antibody (mAb) is a fairly straightforward path to neutralize SARS-CoV. CR3022, a SARS coronavirus-specific human monoclonal antibody, can bind potently with the receptor-binding domain(RBD) of SARS-CoV-2 and has the potential to be developed as candidate therapeutics of SARS-CoV-2 infections [71] .
-- Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. 2020-03-05. | |
| ACE2 mRNA | providing | prerequisite for SARS-CoV-2 infection (count: 1) | |
| ACE2 mRNA is highly expressed and stabilized by B 0 AT1 in gastrointestinal system [3, 4] , providing a prerequisite for SARS-CoV-2 infection.
-- Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020-03-03. | |
| ACE2 protein | supporting | entry of SARS-CoV-2 (count: 1) | |
| Our immunofluorescent data showed that ACE2 protein, which has been proved to be a cell receptor for SARS-CoV-2, is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells.
-- Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020-03-03. | |
| SARS-CoV-2 | bind Hao Zhang ZK to | ACE2 (count: 1) | |
| One possible explanation is that SARS-CoV-2 can bind to ACE2 of intestinal tract (Hao Zhang ZK, Wan et al.,
-- reference not found! | |
| SARS-CoV-2 | use | pig ACE2 proteins (count: 1) | |
| experimentally confirmed that SARS-CoV-2 is able to use human, Chinese horseshoe bat, civet, and pig ACE2 proteins as an entry receptor in ACE2-expressing cells [3] , suggesting that the RBD of SARS-CoV-2 mediates infection in humans and other animals.
-- reference not found! | |
| SARS-CoV-2 S protein | contains | Figure (count: 1) | |
| We found that the SARS-CoV-2 S protein contains a putative furin recognition motif (PRRARSV) (Figure 4 ) similar to that of MERS-CoV, which has a PRSVRSV motif that is likely cleaved by furin [16, 17] during virus egress.
-- reference not found! | |
| SARS-CoV-2 S protein | in domain is | RBD (count: 1) | |
| However, according to the complex structure of human ACE2 and the 138 receptor binding domain (RBD) in SARS-CoV-2 S protein (PDB ID: 6VW1), only 139 three of the eleven sites are located near the interface and potentially mediate the 140 binding, which were T20, Y83 and K353 (Figure 2A) Combining the two screening, we got nine critical aa sites as shown in Figure 2B .
-- reference not found! | |
| 2019-nCoV | use ACE2 as | entry receptor (count: 1) | |
| found that the 2019-nCoV just like SARS-Cov may also use ACE2 as an entry receptor in the ACE2expressing cells, and the majority of which are type II alveolar cells (AT2) in human lung.
-- Coronavirus 2019-nCoV: A brief perspective from the front line. Journal of Infection. 2020-02-25. | |
| We | providing | permission for analysis of spike protein sequence of 2019-nCoV (count: 1) | |
| We thank Dr. Zengli Shi for providing us permission for analysis of the spike protein sequence of 2019-nCoV (GISAID accession no.
-- Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes and Infection. 2020-03-31. | |
| other two works | have reported | ACE2 usage of 2019-nCoV (count: 1) | |
| 4 The other two works have reported or predicted human ACE2 usage of 2019-nCoV in a similar way to SARS-CoV mainly based on the coronavirus spike (S) glycoproteins.
| |
| 2019-nCoV | ACE2 from | primates (count: 1) | |
| 1 , human and non-human primates share the identity sequences in the regions and residues, implying that ACE2 from non-human primates may recognize 2019-nCoV and medi-ate its infection.
| |
| ones | may | With residues in human ACE2 may favorable for 2019-nCoV recognition (count: 1) | |
| With most residues in human ACE2, the ones from these compaion, domestic and wild animals may be favorable for 2019-nCoV recognition, which is in consistent with the recent work by Zheng-Li Shi et al.
| |