Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2

• Published in: Science bulletin (Beijing) Vol. 66; no. 9; pp. 925 - 936
• Main Authors: Gu, Chenjian, Wu, Yang, Guo, Huimin, Zhu, Yuanfei, Xu, Wei, Wang, Yuyan, Zhou, Yu, Sun, Zhiping, Cai, Xia, Li, Yutang, Liu, Jing, Huang, Zhong, Yuan, Zhenghong, Zhang, Rong, Deng, Qiang, Qu, Di, Xie, Youhua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.05.2021; Science China Press. Published by Elsevier B.V. and Science China Press
• Subjects: ACE2; Protoporphyrin IX; SARS-CoV-2; Verteporfin; ACE2; Verteporfin; SARS-CoV-2; Protoporphyrin IX
• ISSN: 2095-9273; 2095-9281
• DOI: 10.1016/j.scib.2020.12.005

[Display omitted] The SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two Food and Drug Administration (FDA)-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 μmol/L and 0.31 μmol/L, respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting a broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human angiotensin-converting enzyme 2 (ACE2). The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2.