ArticleJournal of virology2021
The Polybasic Cleavage Site in SARS-CoV-2 Spike Modulates Viral Sensitivity to Type I Interferon and IFITM2.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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.
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.
Who cites it
112 citing papers in PubMed, 156 citations in OpenAlex.
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.Microbiology spectrum · 2026Trial
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Antibody escape drives emergence of diverse spike haplotypes resembling variants of concern in persistent SARS-CoV-2 infections.Cell reports. Medicine · 2026Article
- IFITM3 at the viral fusion-pore checkpoint: membrane energetics and entry-route-dependent outcomes.Frontiers in immunology · 2026Review
- Neonatal and pediatric thymic grafts generate similar human T-cell chimerism in humanized mice.Frontiers in immunology · 2026Article
- Review
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.bioRxiv : the preprint server for biology · 2025Article
- Viral interferon antagonism shapes host tropism.PLoS pathogens · 2025Review
- Synergistic activation of bat SARS-like coronaviruses spike protein by elastase and TMPRSS2.Scientific reports · 2025Article
- Coronaviruses in wild rodent and eulipotyphlan small mammals: a review of diversity, ecological implications and surveillance considerations.The Journal of general virology · 2025Review
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- The Study of Mutations and Phylogenetics of the SARS-CoV-2 Spike Gene in Population from Tehran Province.Archives of Razi Institute · 2025Article
- Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.Nature communications · 2024Article
- Cellular sialoglycans are differentially required for endosomal and cell-surface entry of SARS-CoV-2 in lung cell lines.PLoS pathogens · 2024Article
- Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection.Viruses · 2024Article
- Review
- A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist.PLoS biology · 2024Article
- The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies.Viruses · 2024Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The cellular entry of severe acute respiratory syndrome-associated coronaviruses types 1 and 2 (SARS-CoV-1 and -2) requires sequential protease processing of the viral spike glycoprotein. The presence of a polybasic cleavage site in SARS-CoV-2 spike at the S1/S2 boundary has been suggested to be a factor in the increased transmissibility of SARS-CoV-2 compared to SARS-CoV-1 by facilitating maturation of the spike precursor by furin-like proteases in the producer cells rather than endosomal cathepsins in the target. We investigate the relevance of the polybasic cleavage site in the route of entry of SARS-CoV-2 and the consequences this has for sensitivity to interferons (IFNs) and, more specifically, the IFN-induced transmembrane (IFITM) protein family that inhibit entry of diverse enveloped viruses. We found that SARS-CoV-2 is restricted predominantly by IFITM2, rather than IFITM3, and the degree of this restriction is governed by route of viral entry. Importantly, removal of the cleavage site in the spike protein renders SARS-CoV-2 entry highly pH and cathepsin dependent in late endosomes, where, like SARS-CoV-1 spike, it is more sensitive to IFITM2 restriction. Furthermore, we found that potent inhibition of SARS-CoV-2 replication by type I but not type II IFNs is alleviated by targeted depletion of IFITM2 expression. We propose that the polybasic cleavage site allows SARS-CoV-2 to mediate viral entry in a pH-independent manner, in part to mitigate against IFITM-mediated restriction and promote replication and transmission. This suggests that therapeutic strategies that target furin-mediated cleavage of SARS-CoV-2 spike may reduce viral replication through the activity of type I IFNs.
Indexed as
Identifiers
What OpenQuestion holds
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.