Molecular interaction

Last updated: 2022 Jul 13
Total hit(s): 76
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Mass spectrometry and kinetic studies have showed that Oridonin binds at the SARS-CoV-2 3CLpro catalytic site by forming a C-S covalent bond and blocks substrate binding through a nonpeptidomimetic covalent binding mode. TSA assay identified SAA (Salvianolic acid A ), EGCG (Epigallocatechin gallate), and Oridonin as potential 3CLpro inhibitors. Oridonin blocks the infectivity of SARS-CoV-2 in Vero E6 cell-based experiments. Solving the co-crystal structure of the 3CLpro-Oridonin complex revealed that Oridonin binds at the 3CLpro catalytic site by forming a CS covalent bond, and blocks substrate binding.
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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

In-vitro biochemical assays show that Nirmatrelvir inhibited wildtype Mpro with a mean Ki of 0.93 nM and the mutated enzymes containing the K90R (Alpha, Beta, Gamma variants) with a Ki 1.05nM, G15S (Lambda variant) with Ki 4.07 nM and P132H (Omicron) with a Ki 0.64 nM. The in-vitro findings imply that PAXLOVID has the ability to sustain plasma nirmatrelvir concentrations several times higher than those required to prevent SARS-CoV-2 VOC/VOI, including Omicron, from multiplying in cells.
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 		Pre-print (bioRxiv)
PMID
~
Title Structural basis for Nirmatrelvir in vitro efficacy against SARS-CoV-2 variants
Impact factor
N/A
Date of Entry 2022 Mar 11

Molecular dynamics (MD) simulations of a linear polyglycerolsulfate (LPGS) with the wild type and Omicron RBDs reveal LPGS binds to the wild type RBD on the cationic patch away from the RBM, whereas it binds to the cationic patch on the RBM of the Omicron RBD. More research is needed to determine if a tighter binding to HSPG may improve the likelihood of binding to ACE2.
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 		35020256
(Chembiochem)
PMID
35020256
Date of Publishing: 2022 Jan 12
Title Charge Matters: Mutations in Omicron variant favor Binding to Cells
Author(s) nameNie C, Sahoo AK et al.
Journal Chembiochem
Impact factor
2.64
Citation count: 3
Date of Entry 2022 Feb 26

The molecular interaction (MI) energy values between the Omicron Spike protein-RBD and ACE2 is 749.8 kcal.mol-1. This is 1.4 times delta variant MI (538.1) and 2.7 times alpha variant MI (276.9). The strong interaction can be contributed to mutations to lysine (K) at N440K, T478K and Q493K in the Omicron variant, which bind to the contact site acidic amino acids of ACE2. Covid-19 variants transmissible strength can be contributed by basic amino acids, especially lysine. Basic amino acids at the interaction site of S-RBD increased the binding affinity with ACE-2.
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 		35026638
(Talanta)
PMID
35026638
Date of Publishing: 2022 Apr 1
Title Quantitative in silico analysis of SARS-CoV-2 S-RBD omicron mutant transmissibility
Author(s) name Hanai T.
Journal Talanta
Impact factor
10.5
Citation count: 5
Date of Entry 2022 Feb 23

Molecular dynamics simulations revealed that the binding energies for two ACE2-RBD(Omicron) structures are lower (-112.25 kcal/mol and -107.04 kcal/mol) than their wild-type counterparts (-104.17 kcal/mol and -97.73 kcal/mol.), indicating stronger binding between ACE2 and RBD(Omicron). Mutations on RBD(Omicron) yield 6.5 ±2.2 hydrogen bonds, residue contacts and larger buried surface(19.1 nm2) at the ACE2-RBD interface. Analyses of RBD-ACE2 interaction are critical for predicting and designing therapeutic antibody efficacy, particularly for developingnew generations of therapeutic antibodies that are able to overcome immune mutant strains.
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 		34968782
(Biochem Biophys Res Commun)
PMID
34968782
Date of Publishing: 2022 Jan 29
Title Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor
Author(s) nameLupala CS, Ye Y et al.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2022 Jan 14

The K417N mutation of Omicron reduces ACE2 binding affinity, but new mutations Q493R, G496S and Q498R, have a compensatory effect on the strength of ACE2 binding and hence Omicron has similar binding affinities of Delta variant. The Omicron spike protein exhibits a measurable increase in affinity for ACE2 relative to the ancestral Wuhan strain, the ACE2 affinity is similar for Delta and Omicron variants.
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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 dissociation constants (KD) for RNA binding to wild type (WT) SARS-CoV-2 N-NTD is 140 mol/L, which is 2000-fold smaller than the value of Y110A mutant (KD = 330 mmol/L). WT SARS-CoV-2 N-NTD has a higher binding affinity to viral derived RNA than mutant in the binding pocket.
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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

2019-nCoV RBD binds with SARS-CoV-specific human monoclonal antibody (CR3022) with a KD of 6.3nM. (1) More research is needed to determine the high-resolution structure of the 2019-nCoV RBD and why it could not be detected by these antibodies.
(2) Some of the most potent SARS-CoV-specific neutralising antibodies (e.g., m396, CR3014) targeting the SARS-CoV receptor binding site failed to bind 2019-nCoV spike protein, indicating that new monoclonal antibodies that bind specifically to 2019-nCoV RBD are required.
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 		32065055
(Emerg Microbes Infect)
PMID
32065055
Date of Publishing: 2020
Title Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
Author(s) nameTian X, Li C et al.
Journal Emerg Microbes Infect
Impact factor
5.84
Citation count: 655
Date of Entry 2021 Nov 20

The RBD of 2019-nCoV S protein binds with human ACE2 with an affinity (KD) 15.2nM which is similar to SARS-CoV and ACE2 binding affinity of 15nM. The RBD of 2019-nCoV is different to that of SARS-CoV. But this did not result in any change with its interaction with ACE2 receptor but had an impact on the cross-reactivity of neutralizing antibodies.
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 		32065055
(Emerg Microbes Infect)
PMID
32065055
Date of Publishing: 2020
Title Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
Author(s) nameTian X, Li C et al.
Journal Emerg Microbes Infect
Impact factor
5.84
Citation count: 655
Date of Entry 2021 Nov 20

SARS-CoV-2 RBD interacts with the N-linked glycan on Asn90 of ACE2 which is absent in SARS-CoV-1.MD simulation of SARS-CoV-2 with ACE2 indicate unbinding forces range from 70 to 105pN and removal of the N-linked glycan reduced unbinding forces to 50-70pN The difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies to block SARS-CoV-2 entry.
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 		32766576
(bioRxiv)
PMID
32766576
Date of Publishing: 2020 Jul 31
Title Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction
Author(s) nameCao W, Dong C et al.
Journal bioRxiv
Impact factor
- n/a -
Citation count: 1
Date of Entry 2021 Oct 30

IgA monoclonal antibody, MAb362, competitively blocks SARS-CoV and SARS-CoV-2 spike proteins and ACE2 receptor binding. The binding affinity of IgA and IgG with RBD of SARS-CoV-2 is 0.3nM and 13nM, respectively. The study of interaction of MAb362 with other receptor blocking and neutralising antibodies against SARS-CoV-2 will help in the development of vaccines and prophylactic/therapeutic antibodies to combat future outbreaks caused by this virus family.
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 		32826914
(Nat Commun)
PMID
32826914
Date of Publishing: 2020 Aug 21
Title A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction
Author(s) nameEjemel M, Li Q et al.
Journal Nat Commun
Impact factor
11.8
Citation count: 62
Date of Entry 2021 Oct 30

MD simulation of the glycosylated trimer spike of SARS-CoV-2 in complex with glycosylated, soluble, human ACE 2 reveals that glycan at N546 of ACE2 interacts with N0074 and N0165 in the S protein. To develop ACE2 as a possible decoy therapy, understanding the influence of ACE2 polymorphisms on glycosylation and S binding is crucial.Modifications of ACE2 glycosylation could lead to more potent biologics that are more competitive inhibitors of S binding.The study provides a foundation for the development of immunogens, vaccines, antibodies, and inhibitors, as well as new information on the mechanisms that allow for glycan microheterogeneity.In order to produce treatments, detailed investigations of the influence of new polymorphisms in S and natural and designed-for-biologics variants of ACE2 on glycosylation and binding properties are necessary.
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 		32743578
(bioRxiv)
PMID
32743578
Date of Publishing: 2020 Jul 24
Title Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
Author(s) nameZhao P, Praissman JL et al.
Journal bioRxiv
Impact factor
- n/a -
Citation count: 1
Date of Entry 2021 Oct 30

The high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM) shows conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. ~
✍
 		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

Molecular interaction studies of SARS-CoV-2 RBD with different variants of hACE2. No major divergence of the interaction interface of SARS-CoV-2 RBD with hACE2
✍
 		32410735
(Biochem Biophys Res Commun)
PMID
32410735
Date of Publishing: 2020 Jun 30
Title Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS -Cov , hot-spot analysis and effect of the receptor polymorphism
Author(s) nameOthman H, Bouslama Z et al.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 69
Date of Entry 2021 Aug 2

Molecular docking studies of Hydroxychloroquine(HCQ) on the RBD of SARS-CoV-2 Spike protein produced a Vina score of −5.5 kcal mol−1 .The hydroxyl group of HCQ molecule forms a strong hydrogen bonding with Asn501 side chain residing on one part of the receptor binding motif (RBM) of the Spike protein. ~
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 		32696720
(J Biomol Struct Dyn)
PMID
32696720
Date of Publishing: 2020 Jul 22
Title Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19
Author(s) name Sehailia M, Chemat S.
Journal J Biomol Struct Dyn
Impact factor
3.22
Citation count: 25
Date of Entry 2021 Aug 2

Seven chimeric peptides (cnCoVP-1, cnCoVP-2, cnCoVP-3, cnCoVP-4, cnCoVP-5, cnCoVP-6, and cnCoVP-7) were found to block SARS-CoV-2 Spike RBD out of 500 generated. The most promising candidates for preventing RBD of the spike are cnCoVP-1 and cnCoVP-4. Chimeric peptides cnCoVP-1 and cnCoVP-4 are found to partially block the access of SARS-CoV-2 Spike RBD to hACE2, howerver further in vitro and in vivo testing and validation is required.
✍
 		32802318
(F1000Res)
PMID
32802318
Date of Publishing: 2020
Title Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain
Author(s) nameBarh D, Tiwari S et al.
Journal F1000Res
Impact factor
2.64
Citation count: 25
Date of Entry 2021 Aug 2

Reporting 7 identifed peptides (DBP1, DBP2, DBP3, DBP4, DBP5, DBP6, DBP7) screened from 5 antimicrobial peptide databases of 20 amino acids in length to target against SARS-CoV-2 Spike RBD to exhibit their anti-SARS virus activities and recognizing DBP6 to be a potential peptide. Peptide DBP6 could be a potential drug peptide to be tested for SARS-CoV-2 Spike protein-drug development.
✍
 		32802318
(F1000Res)
PMID
32802318
Date of Publishing: 2020
Title Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain
Author(s) nameBarh D, Tiwari S et al.
Journal F1000Res
Impact factor
2.64
Citation count: 25
Date of Entry 2021 Aug 2

Reporting 3 designed stretches of hACE2 residue-based peptides (AC26, AC23, AC20) that demonstrates maximum active binding affinity with the Spike SARS-CoV RBD and identifying AC23 and AC20 to be potential sequence based peptide. AC20 and AC23 derived from hACE2 is found to probably block two key critical positions and hence can be further tested for its efficacy and therapeutics target against SARS-CoV-2 Spike RBD
✍
 		32802318
(F1000Res)
PMID
32802318
Date of Publishing: 2020
Title Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain
Author(s) nameBarh D, Tiwari S et al.
Journal F1000Res
Impact factor
2.64
Citation count: 25
Date of Entry 2021 Aug 2

Reporting molecular binding and interaction of tight junction-associated PALS1 structure with Envelope protein C-terminal octapeptides of SARS-CoV and SARS-CoV-2 Key role of E protein C-terminal domain during infection is emphasized.
✍
 		32891874
(Microbes Infect)
PMID
32891874
Date of Publishing: 2020 Nov-Dec
Title Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis
Author(s) nameDe Maio F, Lo Cascio E et al.
Journal Microbes Infect
Impact factor
2.373
Citation count: 28
Date of Entry 2021 Aug 2

Reporting the predicted model of monomeric envelope protein structure of SARS-CoV and SARS-CoV-2 ~
✍
 		32891874
(Microbes Infect)
PMID
32891874
Date of Publishing: 2020 Nov-Dec
Title Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis
Author(s) nameDe Maio F, Lo Cascio E et al.
Journal Microbes Infect
Impact factor
2.373
Citation count: 28
Date of Entry 2021 Aug 2

Comparative analysis of the docking scores obtained by molecular docking of SARS-CoV-2 S1 RBD domain to amyloid and heparin to heparin binding proteins. This shows S1-heparin has the highest docking score and as the temperature increases from 25° C to 40° C, the binding affinity for SARS-CoV-2 S1 protein complexes decreases. Targeting the interaction of SARS-CoV-2 spike protein with the brain proteins might be a suitable way to reduce the aggregation process and thus neurodegeneration in COVID-19 patients.
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 		33789211
(Biochem Biophys Res Commun)
PMID
33789211
Date of Publishing: 2021 May 21
Title SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration
Author(s) name Idrees D, Kumar V.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2021 Aug 12

Heparin binding accelerates the aggregation of pathological amyloid proteins in the brain. Comparative study to the docking score of SARS-CoV-2 S1-heparin complex to amyloid forming proteins shows molecular interaction of the SARS-COV-2 Spike S1 RBD and Heparin shows a high docking score of -282.57. By targeting the binding and aggregation process of the S1 and Heparin, neurodegenration can be prevented.
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 		33789211
(Biochem Biophys Res Commun)
PMID
33789211
Date of Publishing: 2021 May 21
Title SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration
Author(s) name Idrees D, Kumar V.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2021 Aug 12

SARS-CoV-2 S1 RBD binds heparin binding proteins including A, -synuclein, tau, prion, and TDP-43 RRM. The heparin binding site of S1 protein assists the binding to amyloid proteins to the viral surface and initate aggregation of these proteins, leading to neurodegenration in brain. This provides a reasonable explanation for the neurodegenerative distresses caused by a COVID infection. Increase in Kd as the temperature increased from 25 C to 40 C, showed a decrease in binding affinity for SARS-CoV-2 S1 protein complexes.
Increase in temperature usually disrupts the noncovalent interactions between a protein-protein complex, but, the decrease in binding affinity across the temperatures was less apparent for the -Syn complex with S1. This anomaly suggests a stable interaction between -synuclein to SARS-CoV-2 S1 protein.
✍
 		33789211
(Biochem Biophys Res Commun)
PMID
33789211
Date of Publishing: 2021 May 21
Title SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration
Author(s) name Idrees D, Kumar V.
Journal Biochem Biophys Res Commun
Impact factor
2.73
Citation count: 18
Date of Entry 2021 Aug 12

In silico study of bioactive compounds (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) found in Eucalyptus and Corymbia species essential oil on Mpro by molecular docking. The docking study eucaluptol would act as a possible inhibitor of Mpro.
✍
 		33848890
(J Infect Public Health)
PMID
33848890
Date of Publishing: 2021 May
Title Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (M pro) with pharmacokinetics and toxicological properties
Author(s) namePanikar S, Shoba G et al.
Journal J Infect Public Health
Impact factor
2.49
Citation count: 12
Date of Entry 2021 Aug 12

Based on the intermolecular contact maps (COCOMAPS tool) of ACE2-S complex structure, three short peptides (pep1c, pep1d, pep1e) were designed to block virus-host interaction in the early stages of SARS-CoV-2 infection. New therapeutics for oral administration against SARS-CoV-2 infection can be developed using these peptides, which could be an alternative to traditional drug development.
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 		33918595
(Molecules)
PMID
33918595
Date of Publishing: 2021 Apr 9
Title Native Structure-Based Peptides as Potential ProteinProtein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor
Author(s) nameOdolczyk N, Marzec E et al.
Journal Molecules
Impact factor
3.01
Citation count: 8
Date of Entry 2021 Aug 12