Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2

Author:

Xu ZhijianORCID,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 MinORCID,Yang Junling,Du Feifei,Wu Junliang,Wang Peipei,Shen JingshanORCID,Zhang Jianliang,Zheng Yong-TangORCID,Yao HangpingORCID,Zhu WeiliangORCID

Abstract

AbstractEffective 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.

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. A SAR and QSAR study on 3CLpro inhibitors of SARS-CoV-2 using machine learning methods;SAR and QSAR in Environmental Research;2024-07-02

2. Ex Vivo Immunization: A Strategy for Immunization Against SARS-CoV-2;Smart Nanomaterials for Infectious Diseases;2024-03-25

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