Evidence map›Paper›PMID 33755190›Full record

ArticleJournal of cellular physiology2021

Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data.

Abbas Khan, Tauqir Zia, Muhammad Suleman, Taimoor Khan, Syed Shujait Ali, Aamir Ali Abbasi, Anwar Mohammad, Dong-Qing Wei

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cellular physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
224citing papers in PubMed, 3 pooled it
22.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

224 citing papers in PubMed, 3 syntheses or guidelines pooled it, 366 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. COVID-19 pandemic: the delta variant, T-cell responses, and the efficacy of developing vaccines.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Pooled it
  4. Proteome conserved multi-epitope-based vaccine construct against Nipah virus.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Article
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164 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 4 countries.

Abbas KhanDepartment of Bioinformatics and Biological Statistics, Shanghai Jiao Tong University, Shanghai, P.R. China.
Tauqir ZiaDepartment of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan.
Muhammad SulemanCenter for Biotechnology and Microbiology, University of Swat, Swat, Khyber-Pakhtunkhwa, Pakistan.
Taimoor KhanDepartment of Bioinformatics and Biological Statistics, Shanghai Jiao Tong University, Shanghai, P.R. China.
Syed Shujait AliCenter for Biotechnology and Microbiology, University of Swat, Swat, Khyber-Pakhtunkhwa, Pakistan.
Aamir Ali AbbasiNational Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
Anwar MohammadDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait.
Dong-Qing WeiDepartment of Bioinformatics and Biological Statistics, Shanghai Jiao Tong University, Shanghai, P.R. China.ORCID 0000-0003-4200-7502
Shanghai Jiao Tong University · CNQuaid-i-Azam University · PKUniversity of Swat · PKDasman Diabetes Institute · KW

Funding

National Natural Science Foundation of China 2016YFA0501703
6 · The paper itself

Abstract

The evolution of the SARS-CoV-2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor-binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS-CoV-2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y), and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.

Indexed as

Angiotensin-Converting Enzyme 2BrazilCOVID-19HumansMutationProtein BindingSARS-CoV-2South AfricaUnited KingdomVirulenceAngiotensin-Converting Enzyme 2KD (dissociation constant)MD simulationnew variantsprotein-protein dockingSARS-CoV-2

Identifiers

PMID33755190
PMCPMC8251074
OpenAlexW3136193945

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.