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

• 作者: 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
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（9）
• 所属期刊栏目: ARTICLES
• 页码范围: 925-936
• 页数: 12页
• 语种: 英文

摘要

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 tmol/L and 0.31 tmol/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.