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A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.
Ren, Peng-Xuan; Shang, Wei-Juan; Yin, Wan-Chao; Ge, Huan; Wang, Lin; Zhang, Xiang-Lei; Li, Bing-Qian; Li, Hong-Lin; Xu, Ye-Chun; Xu, Eric H; Jiang, Hua-Liang; Zhu, Li-Li; Zhang, Lei-Ke; Bai, Fang.
Afiliación
  • Ren PX; School of Life Science and Technology, and Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
  • Shang WJ; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Yin WC; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Ge H; State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
  • Wang L; School of Life Science and Technology, and Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
  • Zhang XL; School of Life Science and Technology, and Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
  • Li BQ; School of Life Science and Technology, and Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
  • Li HL; Department of Chemistry, Imperial College London, London, United Kingdom.
  • Xu YC; State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
  • Xu EH; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Jiang HL; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhu LL; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zhang LK; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Bai F; School of Life Science and Technology, and Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
Acta Pharmacol Sin ; 43(2): 483-493, 2022 Feb.
Article en En | MEDLINE | ID: mdl-33907306
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antivirales / Diseño de Fármacos / SARS-CoV-2 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antivirales / Diseño de Fármacos / SARS-CoV-2 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China