Molnupiravir Inhibits Porcine Epidemic Diarrhea Virus Infection In Vitro

Viruses. 2023 Jun 2;15(6):1317. doi: 10.3390/v15061317.

Abstract

Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain viral RNA replication. Our study provided evidence for the dose-dependent inhibition of PEDV replication by molnupiravir in Vero cells. Molnupiravir also exhibited a strong inhibitory effect on viral RNA and protein production. Our results demonstrated that molnupiravir inhibits PEDV RNA-dependent RNA polymerase (RdRp) activity and induces a high frequency of mutations in the PEDV genome. Further studies revealed that molnupiravir can reverse changes in the transcriptome caused by viral infection. In conclusion, our results indicated that molnupiravir has the potential to be an effective treatment for PEDV infection.

Keywords: PEDV; RNA-Seq; RdRp activity; antiviral; molnupiravir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Coronavirus Infections* / drug therapy
  • Coronavirus Infections* / veterinary
  • Coronavirus*
  • Hydroxylamines / pharmacology
  • Porcine epidemic diarrhea virus* / genetics
  • Swine
  • Swine Diseases* / prevention & control
  • Vero Cells

Substances

  • molnupiravir
  • Hydroxylamines

Grants and funding

This research was kindly supported by grants from the National Key Research and Development Plans of China (no. 2021YFD1800401), awarded to Zhe Wang, from the National Natural Science Foundation of China (no. 32070128), awarded to Zhe Wang, from the Shanghai Biomedical Science and Technology Support Special Project (no. 21S11900200), awarded to Zhe Wang, and from the Natural Science Foundation of Shanghai (no. 21ZR1433900), awarded to Zhi-Biao Yang.