Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses Targeting Main Protease

Int J Mol Sci. 2021 Nov 9;22(22):12134. doi: 10.3390/ijms222212134.

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 (Mpro) 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.

Keywords: PEDV; SARS-CoV-2; Xanthohumol; coronavirus; natural product.

MeSH terms

  • 3C Viral Proteases / antagonists & inhibitors*
  • 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
  • COVID-19 Drug Treatment
  • Catalytic Domain
  • Chlorocebus aethiops
  • Coronavirus / enzymology
  • Coronavirus / physiology
  • Flavonoids / chemistry*
  • Flavonoids / metabolism
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Humans
  • Molecular Docking Simulation
  • Propiophenones / chemistry*
  • Propiophenones / metabolism
  • Propiophenones / pharmacology
  • Propiophenones / therapeutic use
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use
  • SARS-CoV-2 / enzymology*
  • SARS-CoV-2 / isolation & purification
  • Sequence Alignment
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Biological Products
  • Flavonoids
  • Propiophenones
  • Protease Inhibitors
  • 3C Viral Proteases
  • xanthohumol