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

Chenjian Gu; Yang Wu; Huimin Guo; Yuanfei Zhu; Wei Xu; Yuyan Wang; Yu Zhou; Zhiping Sun; Xia Cai; Yutang Li; Jing Liu; Zhong Huang; Zhenghong Yuan; Rong Zhang; Qiang Deng; Di Qu; Youhua Xie

doi:10.1016/j.scib.2020.12.005

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

Sci Bull (Beijing). 2021 May 15;66(9):925-936. doi: 10.1016/j.scib.2020.12.005. Epub 2020 Dec 9.

Authors

Chenjian Gu¹, Yang Wu¹, Huimin Guo¹, Yuanfei Zhu¹, Wei Xu¹, Yuyan Wang¹, Yu Zhou², Zhiping Sun³, Xia Cai³, Yutang Li¹, Jing Liu¹, Zhong Huang², Zhenghong Yuan¹, Rong Zhang¹, Qiang Deng¹, Di Qu^{1

3}, Youhua Xie^{1

4}

Affiliations

¹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
³ BSL-3 Laboratory of Fudan University, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁴ Children's Hospital, Shanghai Medical College, Fudan University, Shanghai 201102, China.

Abstract

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.

Keywords: ACE2; Protoporphyrin IX; SARS-CoV-2; Verteporfin.