Structure

Last updated: 2022 Jul 13
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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

Cryo-EM structure of monoclonal antibody - T6's Fab in complex with B.1.351 spike trimer protein shows that T6 antibody binds only to the "up" RBD, therefore the T6 epitope is buried when the RBD is in the "down" conformation in the spike trimer. Analysis of T6 epitope residues in the GISAID database revealed a high degree of conservation, thus providing a sequence and structural basis for its broad and potent neutralizing activity against a wide range of SARS-CoV-2 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

X-ray diffraction structures of Nirmatrelvir (PF-07321332) with Mpro of variants of concern having mutations [Alpha, Beta, Gamma(K90R), Lambda (G15S) and Omicron (P132H)], show that the binding of nirmatrelvir is not disturbed by the mutations. The ligand has the same protein interactions as observed in the wild type MPro from the variant USA-WA1/2020. 1. The crystal structures also show that the mutations do not give rise to any signification changes of the protein around the binding pocket or the site of the mutation.
2. The catalytic efficiencies (kcat/Km) of the K90R (28255 S-1M-1), G15S (16483 S-1M-1), and P132H (22692 S-1M-1) are similar to wildtype Mpro (39830 S-1M-1).
3. Nirmatrelvir potently inhibited wildtype (mean Ki of 0.93 nM) and the mutated enzymes containing the K90R (Ki 1.05nM), G15S (Ki 4.07 nM) and P132H (Ki 0.64 nM)Mpro.
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 		~
()
PMID
~
Title Structural basis for Nirmatrelvir in vitro efficacy against SARS-CoV-2 variants
Impact factor
N/A
Date of Entry 2022 Mar 11

Cryo-EM structure of the Omicron variant spike protein in complex with human ACE2 reveals salt bridge between RBD N417 and ACE2 D30 is lost. R493, R498 form salt bridge with ACE2 residues E35, D38, respectively and S496 forms a hydrogen bond with ACE2 residue K353. Compared to the Delta variant, new interactions are formed as a result of the mutations Q493R, G496S and Q498R, and the salt bridge between RBD K417 and ACE2 D30 is lost.
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 		Pre-print (bioRXiv)
Title SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
Impact factor
N/A
Date of Entry 2022 Jan 10

The trimer organisation of the Omicron spike protein ectodomain is similar to that of the original strain and all the earlier variants, according to cryo-EM structural study. The Omicron variant has 37 mutations in the spike protein, and 15 of which are in the receptor binding region (RBD) The Omicron variant spike protein contains 3-5 times the number of mutations found in prior SARS-CoV-2 strains. Understanding the effects of these mutations on ACE2 receptor binding and neutralising antibody evasion is critical for developing effective therapies to stop the spread of the Omicron and related variations.
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 		Pre-print (bioRXiv)
Title SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
Impact factor
N/A
Date of Entry 2022 Jan 10

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.
✍
 		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.
✍
 		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.
✍
 		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.
✍
 		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.
✍
 		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.
✍
 		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 pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure. Here, rabbit 80S ribosome colliding in another ribosome stalled by the SARS-CoV-2 pseudoknot is structurally characterized. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure. By cryo-electron microscopy the structure of rabbit 80S ribosome in complex with eRF1 and ABCE1, stalled at the STOP codon in the mutated SARS-CoV-2 slippery site is studied. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure was studied by cryo-electron microscopy. The rabbit 80S ribosome is stalled close to the mutated SARS-CoV-2 slippery site by a pseudoknot. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure was studied by cryo-electron microscopy to a high resolution. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

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