Antiviral Activity of Probenecid and Oseltamivir on Influenza Virus Replication

Viruses. 2023 Nov 30;15(12):2366. doi: 10.3390/v15122366.

Abstract

Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.

Keywords: BALB/c mice; OAT3 inhibitor; antiviral; influenza; neuraminidase inhibitor; respiratory epithelial cell.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Influenza Vaccines* / therapeutic use
  • Influenza, Human*
  • Mice
  • Neuraminidase
  • Oseltamivir / pharmacology
  • Oseltamivir / therapeutic use
  • Probenecid / pharmacology
  • Probenecid / therapeutic use
  • Virus Replication

Substances

  • Oseltamivir
  • Probenecid
  • Influenza Vaccines
  • Antiviral Agents
  • Enzyme Inhibitors
  • Neuraminidase