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Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.

ABSTRACT: In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperform those modified at the nucleobase. Our in vivo validation using hamster models further bolsters the promise of this nucleoside tailoring approach, positioning it as a valuable asset in the development of innovative antiviral drugs.

SUBMITTER: Min Y

PROVIDER: S-EPMC11006213 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.

Min Yuanqin Y Xiong Wei W Shen Wei W Liu Xingyu X Qi Qianqian Q Zhang Yuanyuan Y Fan Ruochen R Fu Fang F Xue Heng H Yang Hang H Sun Xiulian X Ning Yunjia Y Tian Tian T Zhou Xiang X

Science advances 20240410 15

In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperfor ...[more]

PMID: 38598625

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