Broad-Spectrum Antiviral Drug Candidate Identified to Target Positive-Strand RNA Viruses

Strategic Insights -

Researchers at Hokkaido University have identified a broad-spectrum antiviral drug candidate, 2-thiouridine (s2U), that targets positive-strand RNA viruses, a group of viruses that includes dengue virus, Zika virus, yellow fever virus, and SARS-CoV-2. The drug candidate, a uridine analogue, was found to inhibit viral replication in cell cultures and showed promise in mouse models for dengue and COVID-19. The study's findings were published in the journal Proceedings of the National Academy of Sciences.

Key Takeaways:

  • The researchers screened a library of 753 nucleoside analogs and identified 2-thiouridine (s2U) as a strong inhibitor of viral replication in 10 ssRNA+ viruses, including SARS-CoV-2 Delta and Omicron variants.
  • s2U acted on a specific amino acid in the viral RNA-dependent RNA polymerase (RdRp), inhibiting the synthesis of viral RNA without toxic effects on healthy cells.
  • The drug candidate showed therapeutic efficacy in mice models for dengue and COVID-19, significantly inhibiting viral replication and increasing survival rates.
  • s2U did not have any toxic or mutagenic effects in mice, and its effectiveness was maintained even after multiple intravenous or oral administrations.
  • The researchers concluded that s2U would retain its effectiveness against future variants of SARS-CoV-2.

Statistics:

  • 753 nucleoside analogs were screened for antiviral effects.
  • 10 ssRNA+ viruses were inhibited by s2U, including SARS-CoV-2 Delta and Omicron variants.
  • s2U exhibited a 99% inhibition rate of viral replication in cell cultures.
  • 95% of mice survived in virus-infected groups treated with s2U, compared to 25% in untreated groups.
  • The therapeutic concentration of s2U was maintained for 24 hours in mouse blood plasma after a single intravenous or two oral administrations.

Sources:

  • Proceedings of the National Academy of Sciences (PNAS)
  • Professor Katsumi Maenaka, Hokkaido University
  • Emeritus Professor Akira Matsuda, Hokkaido University
  • Visiting Professor Akihiko Sato, Hokkaido University