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Reviews of "Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis"

Reviewers: Jian Zheng (University of Iowa) | 📗📗📗📗◻️ • Shou-Wei Ding (UC Riverside) |📘📘📘📘📘

Published onMay 19, 2022
Reviews of "Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis"
key-enterThis Pub is a Review of
Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis
Description

AbstractExpanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen with over 16,000 RNAi triggers against the SARS-CoV-2 genome using a massively parallel assay to identify hyper-potent siRNAs. We selected 10 candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity with IC50<20pM and strong neutralisation in live virus experiments. We further enhanced the activity by combinatorial pairing of the siRNA candidates to develop siRNA cocktails and found that these cocktails are active against multiple types of variants of concern (VOC). We examined over 2,000 possible mutations to the siRNA target sites using saturation mutagenesis and identified broad protection against future variants. Finally, we demonstrated that intranasal administration of the siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the Syrian hamster model. Our results pave the way to development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint analyzes the usage of RNAi molecules to create a potent prophylaxis against SARS-COV-2. Reviewers deemed this study strong and reliable with the only potential limitation being the lack of studies in different animal models.

Reviewer 1 (Jian Zheng) | 📗📗📗📗◻️

Reviewer 2 (Shou-Wei Ding) | 📘📘📘📘📘

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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