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Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2.
Xu, Zhijian; Shi, Danrong; Han, Jian-Bao; Ling, Yun; Jiang, Xiangrui; Lu, Xiangyun; Li, Chuan; Gong, Likun; Ge, Guangbo; Zhang, Yani; Zang, Yi; Song, Tian-Zhang; Feng, Xiao-Li; Tian, Ren-Rong; Ji, Jia; Zhu, Miaojin; Wu, Nanping; Wu, Chunhui; Wang, Zhen; Xu, Yechun; Peng, Cheng; Zheng, Min; Yang, Junling; Du, Feifei; Wu, Junliang; Wang, Peipei; Shen, Jingshan; Zhang, Jianliang; Zheng, Yong-Tang; Yao, Hangping; Zhu, Weiliang.
Afiliación
  • Xu Z; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Shi D; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Han JB; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Ling Y; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • Jiang X; Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China.
  • Lu X; Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
  • Li C; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Gong L; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Ge G; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • Zhang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zang Y; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Song TZ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Feng XL; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Tian RR; Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Ji J; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Zhu M; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Wu N; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Wu C; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Wang Z; Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China.
  • Xu Y; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
  • Peng C; Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China.
  • Zheng M; Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China.
  • Yang J; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
  • Du F; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • Wu J; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • Wang P; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • Shen J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zhang J; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zheng YT; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Yao H; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhu W; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Signal Transduct Target Ther ; 8(1): 169, 2023 04 24.
Article en En | MEDLINE | ID: mdl-37095086
Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 µM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 µM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / COVID-19 Tipo de estudio: Clinical_trials / Observational_studies Límite: Animals / Female / Humans / Pregnancy País/Región como asunto: Asia Idioma: En Revista: Signal Transduct Target Ther Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / COVID-19 Tipo de estudio: Clinical_trials / Observational_studies Límite: Animals / Female / Humans / Pregnancy País/Región como asunto: Asia Idioma: En Revista: Signal Transduct Target Ther Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido