Viral protein

Last updated: 2022 Jul 13
Total hit(s): 92
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Original Article
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The crystal structure of T6 Fab bound to the RBD of B.1.351 with three signature mutations K417N/E484K/N501Y (RBD-3M) at 2.89 A resolution, shows that the mutated residues residues N417, K484, and Y501, are not located within the epitope of the T6 Fab. L452R mutation which is found in several SARS-CoV-2 variants, is not evident in the T6 epitope. Examination of the enhancement patterns across the single and triple mutant pseudoviruses showed that the 242244del in NTD, K417N/T, and 417N/484K/501Y in RBD were all potential contributors as mAb T6 was able to exert at least a 3-fold increase in neutralization to 3 of the 4 variants of concern, thus suggesting that its epitope might have become more exposed in some of these variants.
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 		35291264
(iScience)
PMID
35291264
Date of Publishing: 2022 Apr 15
Title RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants
Author(s) nameLiang Q, Wang Y et al.
Journal iScience
Impact factor
4.447
Citation count: 1
Date of Entry 2022 Jul 13

The crystal structure of 3CLpro in complex with Oridonin at a resolution of 2.10 Å shows catalytic residues His41 and Cys145 of 3CLpro interacting with Oridonin. Oridonin inhibits SARSCoV2 3CLpro by forming a covalent bond with the sulfhydryl group of Cys145. Because of Oridonin's nonpeptidomimetic covalent binding mode, it is a novel candidate to develop a new antiviral treatment for COVID-19.
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 		35600064
()
PMID
35600064
Title Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease
Impact factor
N/A
Date of Entry 2022 Jul 13

Structural superimposition of the RBD region of Spike glycoprotein of SARS-CoV-2 wild and its variants - Omicron, Delta AY.1 & 2 and AY. 3, showed structural changes around the antibody binding regions. Protein structure prediction showed Omicron's polarity, non-polarity, and hydrophobicity characteristics changed from the wild SARS-CoV-2. Omicron and Delta AY.3 are expected to be more pathogenic due to their RBD structures' greater instability.
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 		35690234
(Microb Pathog)
PMID
35690234
Date of Publishing: 2022 Jun 8
Title The influence of new SARS-CoV-2 variant Omicron (B.1.1.529) on vaccine efficacy, its correlation to Delta variants: A computational approach
Author(s) nameRanjan P, Neha et al.
Journal Microb Pathog
Impact factor
2.64
Citation count: 1
Date of Entry 2022 Jun 27

Structural analysis was done to show the position of mutated residues in the Lambda spike regions (NTD and RBD). Three mutations (G75V, T76I, and RSYLTPGD246-253N) were presentin theN-terminal domain (NTD)and the deletion mutation (RSYLTPGD246-253N)mutation was observedin a loop structure(loop 5).Another protein region (Receptor binding domain) containstwo mutations (L452Q and F490S). In addition, the T859N mutation wasfound in a specificSpikesubunit (S2heptad repeat 1). Loop 5 contains 246-260 residues, which was a loop structure designated in a previous study.
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 		Pre-print (bioRXiv)
Title SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance
Impact factor
N/A
Date of Entry 2021 Dec 15

A unique drug targeting pocket of 279 ų volume is predicted on the SARS-CoV-2 N-NTD. It has a druggability score between 0 and 1. SARS-CoV N-NTD and MERS-CoV N-NTD pocket volumes similar to SARS-CoV-2N-NTD but HCoV-OC43 has a larger pocket with a volume of 352 3Å ³.
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 		32363136
(Acta Pharm Sin B)
PMID
32363136
Date of Publishing: 2020 Jul
Title Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
Author(s) nameKang S, Yang M et al.
Journal Acta Pharm Sin B
Impact factor
6.15
Citation count: 271
Date of Entry 2021 Nov 8

Structure of SARS-CoV-2 nsp16/nsp10 in complex with RNA cap analogue (m7GpppA) and S-adenosylmethionine (SAM), which methylates 2-OH of ribose of the first transcribing nucleotide of the mRNA cap. It causes conformational changes in nsp16 and an alternate ligand binding site in nsp16 which can be a target for antiviral development. The structure also reveals the basis of an induced fit model of the RNA cap binding and 2-O methylation of the first transcribing nucleotide of SARS-CoV-2 genome.
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 		32709886
(Nat Commun)
PMID
32709886
Date of Publishing: 2020 Jul 24
Title Structural basis of RNA cap modification by SARS-CoV-2
Author(s) nameViswanathan T, Arya S et al.
Journal Nat Commun
Impact factor
11.8
Citation count: 92
Date of Entry 2021 Oct 27

The conformational changes of the spike protein was studied along with the effect of D614G mutation on the soluble S ectodomain construct. The G614 variant exhibited enhanced furin cleavage efficiency and modified RBD constitution. The study used engineered soluble construct. The similarity of these to the native virion context should be studied further. Also, the effect of the D614G mutation on cleavage at the TMPRSS2 cleavage site should be studied.
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 		33417835
(Cell Rep)
PMID
33417835
Date of Publishing: 2021 Jan 12
Title D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction
Author(s) nameGobeil SM, Janowska K et al.
Journal Cell Rep
Impact factor
7.7
Citation count: 98
Date of Entry 2021 Oct 27

The crystal structure of SARS-CoV2 CTD reveals its role in viral RNA binding and its interaction with transcriptional regulatory sequences. 5 unpaired adeno dinucleotide in the stem-loop region of TRS-L is a key factor involved in the binding of nucleocapsid protein It is reported that in SARS-CoV, the N-NTD, N-CTD, and C-IDR domains are to bind the viral RNA. Even so, the roles of them in RNA binding is yet to be determined.
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 		33511102
(Front Chem)
PMID
33511102
Date of Publishing: 2020
Title Structural Insight Into the SARS-CoV-2 Nucleocapsid Protein C-Terminal Domain Reveals a Novel Recognition Mechanism for Viral Transcriptional Regulatory Sequences
Author(s) nameYang M, He S et al.
Journal Front Chem
Impact factor
3.42
Citation count: 20
Date of Entry 2021 Oct 27

The cryo-EM structure of the S protein of the Alpha variant in the apo form and receptor ACE-2 bound form were charecterised. The A570D mutation modulates the opening and closing of the receptor binding domain (RBD) by introducing a salt bridge. The N501Y mutation increases ACE-2 binding affinity by introducing pi-pi interaction.
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 		Pre-print (bioRXiv)
Title Impacts on the structure-function relationship of SARS-CoV-2 spike by B.1.1.7 mutations
Impact factor
N/A
Date of Entry 2021 Sep 13

Structure of SARS-CoV-2 ORF8 accessory protein reveals a 60-residue core.It has is 16% sequence identity to SARS-CoV-2 ORF7a, a covalent disulfide linked dimer and a non-covalent dimer formed by 73YIDI76 sequence. ORF8 antibodies are major serological markers of SARS-CoV-2 infection.
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 		33361333
(Proc Natl Acad Sci U S A)
PMID
33361333
Date of Publishing: 2021 Jan 12
Title Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion
Author(s) nameFlower TG, Buffalo CZ et al.
Journal Proc Natl Acad Sci U S A
Impact factor
9.35
Citation count: 84
Date of Entry 2021 Aug 22

Neuropilin-1 b1 domain binds with SARS-CoV-2 S1 C-end rule (CendR) peptide (7 residues -679-NSPRRAR-685) with an affinity of 20.3 µM at pH 7.5, and 13.0 µM at pH 5.5. In NRP1-depleted Caco-2 cells, viral uptake is halved compared to control cells. Blocking the interaction of NRP1-b1 with SARS-CoV-2 S1 CendR with inhibitors like EG00229 can lead to new anti COVID-19 therapeutics.
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 		33082294
(Science)
PMID
33082294
Date of Publishing: 2020 Nov 13
Title Neuropilin-1 is a host factor for SARS-CoV-2 infection
Author(s) nameDaly JL, Simonetti B et al.
Journal Science
Impact factor
20.57
Citation count: 477
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease with Uridine-2',3'-Vanadate (UV, a transition state analog), results in the formation of 2′,3′-cyclic phosphodiester. This is critical for further RNA maturation and functions. This structure proposes that Nsp15 should follow a two-step reaction mechanism with the final product being 3UMP.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Impact factor
N/A
Citation count: 34
Date of Entry 2021 Aug 2

The structure of Tipiracil (a uracil derivative ) and SARS-CoV-2 Nsp15 endoribonuclease shows Tipiracil competitively inhibits the enzyme action by binding to its active site. Structure illustrates that uracil alone probably has similar inhibitory properties and provides basis for the uracil scaffold-based drug development.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Impact factor
N/A
Citation count: 34
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease in complex with dinucleoside monophosphate (GpU), which binds to the active site of the enzyme with uracil interacting with Tyr343 and Ser294. This results in the SARS-CoV-2 Nsp15 is inhibition. Complex structure demonstrates location and specificity determinants of the uridine with a 5-phosphoryl group. Nsp15 is shown to bind and hydrolyze 4, 7, and 20 nucleotide long RNA. Comparitive study of Nsp15 and RNase A active site displayed some conserved active site residues and indicated a common catalytic mechanism with a two-step reaction releasing 3UMP, despite distinct RNA binding site organization in both including both sequence and structure dissimilarity.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Impact factor
N/A
Citation count: 34
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease in complex with 3'-uridine monophosphate shows uracil demonstrates higher affinity for Trp333 site than in uracil-recognition site created by His235, His250, and Thr341. Structure emphasis that since the enzyme's substrate is a larger RNA molecule, the identity of the Trp333-interacting base is inappropriate.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Impact factor
N/A
Citation count: 34
Date of Entry 2021 Aug 2

SARS-CoV-2 Nsp15 is inhibited by interactions with the uridine binding pocket in the enzyme's active site. Structure of SARS CoV-2 Nsp15 endoribonuclease in complex with Uridine-5'-Monophosphate shows Nsp15 discriminates between the uracil and purine bases by forming van der Waals contacts with Tyr343 and hydrogen bonds Ser294 (an active site residue ). Nsp15 enzyme is inhibited by the binding of 5'-UMP in the uracil binding pocket.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Impact factor
N/A
Citation count: 34
Date of Entry 2021 Aug 2

Monovalent hACE2 decoy CTC-445.2 binds to all the three RBDs of a single spike protein with a low nanomolar affinity and high specificity. The divalent CTC-445.2d shows about ~10 fold increase in the binding. De novo protein design approach to generate decoys is independent to traditional therapeutics and has the potential to better overcome mutational viral evasion.
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 		33154107
(Science)
PMID
33154107
Date of Publishing: 2020 Dec 4
Title De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
Author(s) nameLinsky TW, Vergara R et al.
Journal Science
Impact factor
20.57
Citation count: 75
Date of Entry 2021 Jul 28

Structure of SARS-CoV-2 RNA-dependent RNA polymerase nsp12 in complex with cofactors nsp7 and nsp8 under reducing condition, forms a β hairpin domain (residues N215 to N218) at its N-terminus. This structure aids in antiviral viral study of remdesivir and other antiviral drugs. The structure of RdRp can be used as a source for discovering broad spectrum antivirals.
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 		32277040
(Science)
PMID
32277040
Date of Publishing: 2020 May 15
Title Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Author(s) nameGao Y, Yan L et al.
Journal Science
Impact factor
20.57
Citation count: 592
Date of Entry 2021 Jul 28

Structure of SARS-Cov-2 RNA-dependent RNA polymerase nsp12, in complex with nsp7 and nsp8 reports a conserved polymerase core and a β hairpin domain (residues N215 to N218) at its N-terminus. This structure aids in the study of remdesivir and other drug candidates' antiviral activity. The structure of RdRp can be used as a source for discovering broad spectrum antivirals.
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 		32277040
(Science)
PMID
32277040
Date of Publishing: 2020 May 15
Title Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Author(s) nameGao Y, Yan L et al.
Journal Science
Impact factor
20.57
Citation count: 592
Date of Entry 2021 Jul 28

Binding of monoclonal antibody, B6-Fab to SARS-CoV/SARS-CoV-2 spike stem helix peptide, sterically interferes with the spike protein's fusion of the membrane. B6 binds to the hydrophobic core of the stem helix bundle and disrupts its quaternary structure. It prevents S2 subunit refolding from the pre- to the post-fusion state and blocks viral entry. This study unveils an unexpected target for next-generation structure-guided design of a pan-beta-coronavirus vaccine.
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 		33981021
(Nat Struct Mol Biol)
PMID
33981021
Date of Publishing: 2021 May 12
Title Structural basis for broad coronavirus neutralization
Author(s) nameSauer MM, Tortorici MA et al.
Journal Nat Struct Mol Biol
Impact factor
9.8
Citation count: 46
Date of Entry 2021 Jul 28

Structural characterization of SARS-CoV-2S 2P trimer complexed with C105 Fabs, state 2 (3RBD "up") shows mutations in the spike protein do not effect the RBD-binding of mAb C105. Anti-SARS-CoV-2 antibody class derived form VH3-53/VH3-66 have a structural basis for eliciting neutralizing antibodies. The RBD and S1A epitopes are not affected by the common mutations in various SARS_CoV-2 isolates, so the various vaccines and antibody therapeutics would be effective against the COVID-19.
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 		32645326
(Cell)
PMID
32645326
Date of Publishing: 2020 Aug 20
Title Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
Author(s) nameBarnes CO, West AP Jr et al.
Journal Cell
Impact factor
27.35
Citation count: 387
Date of Entry 2021 Jul 28

Polycolonal IgGs and Fabs from COVID-19 convalescent patients recognise different RBD epitopes of different coronaviruses. Structural characterization of SARS-CoV-2S 2P trimer complexed with C105 Fabs, state 1 (2RBD "up"), recognises both S1A and RBD epitopes on SARS-CoV-2 spike. It reveals an epitope that blocks ACE2 receptor binding. Mutations in the spike protein do not effect the RBD-binding mAb C105. The RBD and S1A epitopes are not affected by the common mutations in various SARS_CoV-2 isolates, so the various vaccines and antibody therapeutics would be effective against the COVID-19.
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 		32645326
(Cell)
PMID
32645326
Date of Publishing: 2020 Aug 20
Title Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
Author(s) nameBarnes CO, West AP Jr et al.
Journal Cell
Impact factor
27.35
Citation count: 387
Date of Entry 2021 Jul 28

Neutralizing antibodies (nAbs) from SARS-CoV-2 patients encoded by antibody families (IGHV3-53/3-66 and IGHV1-2) bind the RBS in two different binding modes, but E484K or K417N mutation evades their binding and neutralization. The CR3022 cryptic site and S309 site are promising targets to avoid interference by SARS-CoV-2 mutations observed to date.
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 		Pre-print (bioRXiv)
Title Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
Author(s) name -
Impact factor
N/A
Date of Entry 2021 Jun 14

Structure of SARS-CoV-2 spike receptor binding domain (RBD) using computational methods predicts antibody RBD recognition signatures which can be used to design vaccine against Covid-19. In this study the effects from RBD substitutions on ACE2 recognition were not considered.
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 		Pre-print (bioRXiv)
Title Structural and energetic profiling of SARS-CoV-2 antibody recognition and the impact of circulating variants
Author(s) name -
Impact factor
N/A
Date of Entry 2021 Jun 14

Structural characterization of the SARS-CoV-2 N501Y mutant spike protein ectodomain. Y501 inserts into a cavity at the binding interface near Y41 of ACE2 and this interaction causes the increased ACE2 affinity (3- to 16-fold) in ACE2 binding and its increased infectivity. The cryo-EM methods to identify the footprints of antibodies produced byt the vaccinesis a critical tool to prevent and treact COVID-19.
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 		33914735
(PLoS Biol)
PMID
33914735
Date of Publishing: 2021 Apr 29
Title Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies
Author(s) nameZhu X, Mannar D et al.
Journal PLoS Biol
Impact factor
7.62
Citation count: 68