Evidence map›Paper›PMID 36583790›Full record

ArticleMedical microbiology and immunology2023

Intrinsic D614G and P681R/H mutations in SARS-CoV-2 VoCs Alpha, Delta, Omicron and viruses with D614G plus key signature mutations in spike protein alters fusogenicity and infectivity.

Ritika Khatri, Gazala Siddqui, Srikanth Sadhu, Vikas Maithil, Preeti Vishwakarma, Bharat Lohiya, Abhishek Goswami, Shubbir Ahmed, Amit Awasthi, Sweety Samal

Abstract read
In one paragraph

Article in Medical microbiology and immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
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

34 citing papers in PubMed.

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  16. Dynamics of SARS-CoV-2 variants in West Africa: Insights into genomic surveillance in resource-constrained settings.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2024
    Review
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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

10 authors.

Ritika KhatriTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Gazala SiddquiTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Srikanth SadhuTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Vikas MaithilTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Preeti VishwakarmaTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Bharat LohiyaTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Abhishek GoswamiTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Shubbir AhmedCentralized Core Research Facility (CCRF), All India Institute of Medical Science (AIIMS), Delhi, India.
Amit AwasthiTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India.
Sweety SamalTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India. sweety.samal@thsti.res.in.ORCID http://orcid.org/0000-0001-7894-8756

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The SARS-CoV-2 virus has been rapidly evolving over the time and the genetic variation has led to the generation of Variants of Concerns (VoC), which have shown increased fitness. These VoC viruses contain the key mutations in the spike protein which have allowed better survival and evasion of host defense mechanisms. The D614G mutation in the spike domain is found in the majority of VoC; additionally, the P681R/H mutation at the S1/S2 furin cleavage site junction is also found to be highly conserved in major VoCs; Alpha, Delta, Omicron, and its' current variants. The impact of these genetic alterations of the SARS-CoV-2 VoCs on the host cell entry, transmissibility, and infectivity has not been clearly identified. In our study, Delta and D614G + P681R synthetic double mutant pseudoviruses showed a significant increase in the cell entry, cell-to-cell fusion and infectivity. In contrast, the Omicron and P681H synthetic single mutant pseudoviruses showed TMPRSS2 independent cell entry, less fusion and infectivity as compared to Delta and D614G + P681R double mutants. Addition of exogenous trypsin further enhanced fusion in Delta viruses as compared to Omicron. Furthermore, Delta viruses showed susceptibility to both E64d and Camostat mesylate inhibitors suggesting, that the Delta virus could exploit both endosomal and TMPRSS2 dependent entry pathways as compared to the Omicron virus. Taken together, these results indicate that the D614G and P681R/H mutations in the spike protein are pivotal which might be favoring the VoC replication in different host compartments, and thus allowing a balance of mutation vs selection for better long-term adaptation.

Indexed as

COVID-19SARS-CoV-2HumansMutationSpike Glycoprotein, CoronavirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2DeltaInfectivityOmicronSARS-CoV-2 variants of concernVirus entry

Identifiers

PMID36583790
PMCPMC9801140

What OpenQuestion holds

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LicenceCC BY
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.