PT  - JOURNAL ARTICLE
AU  - Chenjian Gu
AU  - Yang Wu
AU  - Huimin Guo
AU  - Yuanfei Zhu
AU  - Wei Xu
AU  - Yuyan Wang
AU  - Yu Zhou
AU  - Zhiping Sun
AU  - Xia Cai
AU  - Yutang Li
AU  - Jing Liu
AU  - Zhong Huang
AU  - Zhenghong Yuan
AU  - Rong Zhang
AU  - Qiang Deng
AU  - Di Qu
AU  - Youhua Xie
TI  - Protoporphyrin IX and verteporfin prevent SARS-CoV-2 infection <em>in vitro</em> and in a mouse model expressing human ACE2
AID  - 10.1101/2020.04.30.071290
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.30.071290
4099  - http://biorxiv.org/content/early/2020/07/30/2020.04.30.071290.short
4100  - http://biorxiv.org/content/early/2020/07/30/2020.04.30.071290.full
AB  - 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 FDA-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 μM and 0.31 μM 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 broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human 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.Competing Interest StatementThe authors have declared no competing interest.