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

• Published in: Signal transduction and targeted therapy 2023-04, Vol.8 (1), p.169-8, Article 169
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 692/308/575; 692/4017; Animals; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Cancer Research; Cell Biology; China; Coronaviruses; COVID-19; Female; HIV; HIV Infections; Human immunodeficiency virus; Humans; Internal Medicine; Macaca mulatta; Medicine; Medicine & Public Health; Necropsy; Nelfinavir; Nelfinavir - pharmacology; Oncology; Pathology; Patients; Pregnancy; Prospective Studies; Public health; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-023-01429-0

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 (IC 50  = 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 (EC 50 ). 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.