ArticleProceedings of the National Academy of Sciences of the United States of America2026
Evaluation of a proposed link between the SARS-CoV-2 furin cleavage site and mouse-adapted MERS-coronavirus MA30.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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
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Who cites it
1 citing paper in PubMed.
- Evaluation of a proposed link between the SARS-CoV-2 furin cleavage site and mouse-adapted MERS-coronavirus MA30.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
The origin of the polybasic furin cleavage site (FCS) of SARS-CoV-2 remains a central question in debates on the emergence of COVID-19. One hypothesis proposes a genetic relationship between the SARS-CoV-2 S1/S2 motif RRAR and the RRVR sequence found in the mouse-adapted MERS-CoV strain MERS-MA30. Here, we combined large-scale bioinformatic analysis with experimental virology to evaluate this scenario. Analysis of over 17 million SARS-CoV-2 genomes revealed that the S:684V substitution corresponding to RRVR occurred repeatedly but only sporadically, never became phylogenetically basal, and showed limited geographic and temporal spread. Using reverse genetics, we generated SARS-CoV-2 variants encoding RRVR and demonstrated that S:684V consistently reduced viral entry efficiency and competitive fitness in multiple cell systems, including human respiratory epithelial cultures. RRVR variants did not evolve toward RRAR but instead accumulated alternative substitutions. These findings do not support an evolutionary relationship between MERS-MA30 and the SARS-CoV-2 FCS.
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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 Socratic graph.