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A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

ABSTRACT: The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC₅₀ values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

SUBMITTER: Ren PX

PROVIDER: S-EPMC8076879 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

Ren Peng-Xuan PX Shang Wei-Juan WJ Yin Wan-Chao WC Ge Huan H Wang Lin L Zhang Xiang-Lei XL Li Bing-Qian BQ Li Hong-Lin HL Xu Ye-Chun YC Xu Eric H EH Jiang Hua-Liang HL Zhu Li-Li LL Zhang Lei-Ke LK Bai Fang F

Acta pharmacologica Sinica 20210427 2

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lyc ...[more]

PMID: 33907306

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