1. Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses Targeting Main Protease.
- Author
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Lin Y, Zang R, Ma Y, Wang Z, Li L, Ding S, Zhang R, Wei Z, Yang J, and Wang X
- Subjects
- 3C Viral Proteases chemistry, 3C Viral Proteases metabolism, Alphacoronavirus enzymology, Alphacoronavirus physiology, Amino Acid Sequence, Animals, Binding Sites, Biological Products chemistry, Biological Products metabolism, Biological Products pharmacology, Biological Products therapeutic use, COVID-19 virology, Catalytic Domain, Chlorocebus aethiops, Coronavirus enzymology, Coronavirus physiology, Flavonoids metabolism, Flavonoids pharmacology, Flavonoids therapeutic use, Humans, Molecular Docking Simulation, Propiophenones metabolism, Propiophenones pharmacology, Propiophenones therapeutic use, Protease Inhibitors metabolism, Protease Inhibitors pharmacology, Protease Inhibitors therapeutic use, SARS-CoV-2 isolation & purification, Sequence Alignment, Vero Cells, Virus Replication drug effects, COVID-19 Drug Treatment, 3C Viral Proteases antagonists & inhibitors, Flavonoids chemistry, Propiophenones chemistry, Protease Inhibitors chemistry, SARS-CoV-2 enzymology
- Abstract
Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (M
pro ) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, we report that Xanthohumol, a small molecule in clinical trials from hops ( Humulus lupulus ), was a potent pan-inhibitor for various coronaviruses by targeting Mpro , for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 μM), and alphacoronavirus PEDV (IC50 value of 7.51 μM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.- Published
- 2021
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