RT Journal Article SR Electronic T1 Protoporphyrin IX and verteporfin prevent SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.30.071290 DO 10.1101/2020.04.30.071290 A1 Chenjian Gu A1 Yang Wu A1 Huimin Guo A1 Yuanfei Zhu A1 Wei Xu A1 Yuyan Wang A1 Yu Zhou A1 Zhiping Sun A1 Xia Cai A1 Yutang Li A1 Jing Liu A1 Zhong Huang A1 Zhenghong Yuan A1 Rong Zhang A1 Qiang Deng A1 Di Qu A1 Youhua Xie YR 2020 UL http://biorxiv.org/content/early/2020/07/30/2020.04.30.071290.abstract 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.