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The signature of SARS-CoV-2 evolution reflects selective pressures within human guts
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  • Ancha Baranova,
  • Zhiyanov A.,
  • Shkurnikov M.,
  • Nersisyan A.,
  • Cai H.,
  • Tonevitsky A.
Ancha Baranova
George Mason University School of Systems Biology

Corresponding Author:abaranov@gmu.edu

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Zhiyanov A.
Nacional'nyj issledovatel'skij universitet Vyssaa skola ekonomiki Fakul'tet biologii i biotehnologii
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Shkurnikov M.
Nacional'nyj issledovatel'skij universitet Vyssaa skola ekonomiki Fakul'tet biologii i biotehnologii
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Nersisyan A.
Nacional'nyj issledovatel'skij universitet Vyssaa skola ekonomiki Fakul'tet biologii i biotehnologii
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Cai H.
Sun Yat-sen University - Shenzhen Campus
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Tonevitsky A.
Nacional'nyj issledovatel'skij universitet Vyssaa skola ekonomiki Fakul'tet biologii i biotehnologii
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Abstract

In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. Here we demonstrate that a significant number of miRNA binding sites locate in the NSP4 region of the SARS-CoV-2 genome, and the intestinal human miRNAs exert evolutionary pressure on this region. Notably, in infected cells, NSP4 promotes the formation of double-membrane vesicles, which serve as the scaffolds for replication-transcriptional complexes and protect viral RNA from intracellular destruction. In three years of selection, the loss of many miRNA binding sites, in particular, those within the NSP4, has shaped the SARS-CoV-2 genomes to promote the descendants of the BA.2 variants as the dominant strains that define current momentum of the pandemics. Findings highlight the possibility that intestinal tissue may significantly impact evolution of the SARS-CoV-2 genome and may play a pivotal role in the long COVID.
07 Apr 2023Submitted to Journal of Medical Virology
07 Apr 2023Submission Checks Completed
07 Apr 2023Assigned to Editor
07 Apr 2023Review(s) Completed, Editorial Evaluation Pending
07 Apr 2023Reviewer(s) Assigned
15 May 2023Editorial Decision: Revise Major
10 Jun 20231st Revision Received
10 Jul 2023Submission Checks Completed
10 Jul 2023Assigned to Editor
10 Jul 2023Review(s) Completed, Editorial Evaluation Pending
17 Jul 2023Editorial Decision: Accept