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February 11, 2022Proceedings of the National Academy of SciencesOpen Access

Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion

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Why the study?

How SARS-CoV-2 circumvents Nsp1-mediated suppression of host protein synthesis to enable viral translation, and whether this mechanism can be targeted therapeutically, remained unclear.

Population

Transgenic mice expressing human ACE2 and in vitro models

Comparison

Locked nucleic acid antisense oligonucleotides targeting stem-loop 1 vs control

Design

Preclinical in vitro and in vivo study

Authors

SVSetu M. VoraPFPietro FontanaTMTianyang Mao

Discussion

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Member takes

Overview

Should not yet change COVID-19 care; leaves open human translation of SL1-targeted ASOs.

Structured PICO

P
Population
In vitro cell lines (HeLa, HEK293T, Vero E6) and K18-hACE2 transgenic mice (n=10 per group) infected with SARS-CoV-2
I
Intervention
Antisense oligonucleotides (ASOs) targeting stem-loop 1 (SL1) of the SARS-CoV-2 5' UTR (e.g., ASO4 400 μg intranasally daily for 4 days in mice)
C
Comparator
Control (scrambled) ASO
O
Outcome
Viral translation, viral replication in vitro, and survival/weight loss in vivosurrogate

Targeting the SL1 region of the SARS-CoV-2 5' UTR with antisense oligonucleotides inhibits viral translation and protects against SARS-CoV-2-induced lethality in a mouse model.

Cite This Study

Vora et al. (2022) studied this question.

synapsesocial.com/papers/6a7ff50fa89a13a921d475a7https://doi.org/10.1073/pnas.2117198119
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