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Reviews of "Antisense oligonucleotides target a nearly invariant structural element from the SARS-CoV-2 genome and drive RNA degradation"

Reviewers: Hasan Cubuk (Istanbul Arel University) | 📗📗📗📗 ◻️ • Anders Näär (UC Berkeley) | 📒📒📒 ◻️ ◻️ • Valerio Orlando (KAUST) | 📒📒📒 ◻️ ◻️

Published onNov 05, 2020
Reviews of "Antisense oligonucleotides target a nearly invariant structural element from the SARS-CoV-2 genome and drive RNA degradation"
key-enterThis Pub is a Review of
Antisense oligonucleotides target a nearly invariant structural element from the SARS-CoV-2 genome and drive RNA degradation
Antisense oligonucleotides target a nearly invariant structural element from the SARS-CoV-2 genome and drive RNA degradation
Description

Summary The SARS-CoV-2 virus contains an unusually large, single-stranded RNA genome that is punctuated with structured elements of unknown function, such as the s2m element located in the 3’ untranslated region. The evolutionary conservation of the s2m element and its occurrence in all viral subgenomic transcripts implicates a key role in the viral infection cycle. In order to exploit this element as a potential therapeutic target, we have designed antisense “gapmer” oligonucleotides that efficiently base-pair to the s2m region. These oligonucleotides, composed of locked nucleic acids (LNA) flanking a central DNA core, successfully remodel the s2m structure and induce sequence-specific RNA cleavage by RNase H in vitro. Gapmers are also effective in human cells as they reduce the fluorescence signal in GFP reporter assays and cause a dose-dependent reduction in replication in a model replicon system based on a human astrovirus. Overall, these oligonucleotides show promise as anti-viral agents and may serve as a helpful starting point to develop treatments for COVID-19.

To read the original manuscript, click the link above.

Summary of Reviews: This manuscript offers a gapmer-based therapeutic strategy targeting the highly conserved s2m element present in the SARS-CoV-2 genome. While potentially informative, the study's claims require testing with wildtype SARS-CoV-2 virus and animal models to be substantiated.

Reviewer 1 (Hasan Cubuk) | 📗📗📗📗◻️

Reviewer 2 (Anders Näär) | 📒📒📒 ◻️◻️

Reviewer 3 (Valerio Orlando) | 📒📒📒 ◻️◻️

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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