Journal
SCIENCE BULLETIN
Volume 66, Issue 9, Pages 925-936Publisher
ELSEVIER
DOI: 10.1016/j.scib.2020.12.005
Keywords
SARS-CoV-2; ACE2; Protoporphyrin IX; Verteporfin
Categories
Funding
- National Science and Technology Major Project (NSTMP) for the Prevention and Treatment of Infectious Diseases [2018ZX10734401, 2018ZX10301208]
- NSTMP for the Development of Novel Drugs [2019ZX09721001]
- Project of Novel Coronavirus Research of Fudan University, China Postdoctoral Science Foundation [2020T130016ZX]
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The study found that protoporphyrin IX and verteporfin are effective antiviral agents against SARS-CoV-2 infection, inhibiting the cytopathic effect and preventing viral binding to the receptor.
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 mu mol/L and 0.31 mu mol/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. (c) 2020 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
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