ArticlePLoS pathogens2021
SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
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- Viral syncytia evolve to resist interferon.Nature communications · 2026Article
- Universal and quantitative detection of double-stranded RNAs as a signature of pan-virus infections using a luciferase-based biosensor.Journal of biological engineering · 2025Article
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- Long-Circulating Nanobody Confers Durable Prophylaxis against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Infection.Advanced nanobiomed research · 2025Article
- Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution.Journal of virology · 2025Article
- Current status and future prospects of toxicity assessment using organoids.Toxicological research · 2025Review
- SARS-CoV-2 biological clones are genetically heterogeneous and include clade-discordant residues.Journal of virology · 2025Article
- Structural basis of TMPRSS11D specificity and autocleavage activation.Nature communications · 2025Article
- Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.Viruses · 2025Review
- Application of versatile reverse genetics system for feline coronavirus.Microbiology spectrum · 2025Article
- A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a.EBioMedicine · 2025Article
- Malabaricone C isolated from edible plants as a potential inhibitor of SARS-CoV-2 infection.Scientific reports · 2025Article
- The recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells.Virus evolution · 2025Article
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- Kinetic Landscape of Single Virus-like Particles Highlights the Efficacy of SARS-CoV-2 Internalization.Viruses · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains.
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Registered trials
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.