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Reviews of "A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats"

Reviewers: Margo Brinton (Georgia State University) | 📗📗📗📗◻️ • Alexei Korennykh (Princeton) | 📗📗📗📗◻️• Roy Parker (University of Colorado) | 📘📘📘📘📘 • James Burke (University of Colorado) | 📘📘📘📘📘

Published onSep 16, 2021
Reviews of "A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats"
key-enterThis Pub is a Review of
A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats
Description

Abstract Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission and disease severity. To better understand the antiviral response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that while some people can express a prenylated OAS1 variant, that is membrane-associated and blocks SARS-CoV-2 infection, other people express a cytosolic, nonprenylated OAS1 variant which does not detect SARS-CoV-2 (determined by the splice-acceptor SNP Rs10774671). Alleles encoding nonprenylated OAS1 predominate except in people of African descent. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response. Remarkably, approximately 55 million years ago, retrotransposition ablated the OAS1 prenylation signal in horseshoe bats (the presumed source of SARS-CoV-2). Thus, SARS-CoV-2 never had to adapt to evade this defense. As prenylated OAS1 is widespread in animals, the billions of people that lack a prenylated OAS1 could make humans particularly vulnerable to the spillover of coronaviruses from horseshoe bats.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint colleagues perform a screen to identify interferon-stimulated genes that inhibit SARS-CoV-2 replication. The authors deem the study design as reliable and recommended only minor revisions.

Reviewer 1 (Margo Brinton) | 📗📗📗📗◻️

Reviewer 2 (Alexei Korennykh ) | 📗📗📗📗◻️

Reviewer 3 (Roy Parker, James Burke) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 


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