An orally active entry inhibitor of influenza A viruses protects mice and synergizes with oseltamivir and baloxavir marboxil

Irina Gaisina, Ping Li, Ruikun Du, Qinghua Cui, Meiyue Dong, Chengcheng Zhang, Balaji Manicassamy, Michael Caffrey, Terry Moore, Laura Cooper, Lijun Rong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are several approved drugs targeting different mechanisms, the emergence of drug resistance calls for new drug candidates that can be used alone or in combinations. Small-molecule IAV entry inhibitor, ING-1466, binds to hemagglutinin (HA) and blocks HA-mediated viral infection. Here, we show that this inhibitor demonstrates preventive and therapeutic effects in a mouse model of IAV with substantial improvement in the survival rate. When administered orally it elicits a therapeutic effect in mice, even after the well-established infection. Moreover, the combination of ING-1466 with oseltamivir phosphate or baloxavir marboxil enhances the therapeutic effect in a synergistic manner. Overall, ING-1466 has excellent oral bioavailability and in vitro absorption, distribution, metabolism, excretion, and toxicity profile, suggesting that it can be developed for monotherapy or combination therapy for the treatment of IAV infections.

Original languageEnglish
Article numbereadk9004
JournalScience advances
Volume10
Issue number8
DOIs
StatePublished - Feb 2024
Externally publishedYes

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