AMPK inhibitor, compound C, inhibits coronavirus replication in vitro

PLoS One. 2023 Oct 3;18(10):e0292309. doi: 10.1371/journal.pone.0292309. eCollection 2023.

Abstract

The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control and AMPK-knockout (KO) cells and found that the virus replication decreased in AMPK-KO cells. Next, we examined the effect of the AMPK inhibitor, compound C on coronavirus replication. Compound C treatment efficiently inhibited the replication and decreased the coronavirus-induced cytotoxicity, further inhibiting autophagy. In addition, treatment with compound C in combination with chloroquine synergistically inhibited coronavirus replication. These results suggest that compound C can be considered as a potential drug candidate for COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • Antiviral Agents* / pharmacology
  • Coronavirus OC43, Human* / drug effects
  • Humans
  • Pyrazoles / pharmacology
  • Virus Replication / drug effects

Substances

  • AMP-Activated Protein Kinases
  • Antiviral Agents
  • dorsomorphin
  • Pyrazoles

Grants and funding

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2019R1A2C1006511). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.