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Reviews of "Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses"

Reviewers: Ewan Plant (US FDA) | 📗📗📗📗◻️  •  Yitzhak Pilpel (Weizmann Institute) | 📘📘📘📘📘

Published onDec 05, 2021
Reviews of "Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses"
key-enterThis Pub is a Review of
Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses
Description

Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored a group of 6 small-molecule ligands, evaluating their activity against the frameshift signals from a panel of representative bat CoVs—the most likely source of future zoonoses—as well as SARS-CoV-2 and MERS-CoV. We found that whereas some ligands had notable activity against only a few of the frameshift signals, the serine protease inhibitor nafamostat suppressed −1 PRF significantly in several of them, while having limited to no effect on −1 PRF caused by frameshift signals from other viruses used as negative controls. These results suggest it is possible to find small-molecule ligands that inhibit −1 PRF specifically in a broad spectrum of CoVs, establishing the frameshift signal as a viable target for developing pan-coronaviral therapeutics.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint examines the therapeutic potential of small molecule ligands that inhibit ribosomal frameshifting. The authors find the tested ligands inhibit ribosomal frameshifting in vitro for a panel of coronaviruses and reviewers find the preprint's strength of evidence strong.

Reviewer 1 (Ewan Plant) | 📗📗📗📗◻️

Reviewer 2 (Yitzhak Pilpel) | 📘📘📘📘📘

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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