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

doi:10.1126/sciadv.adk9004

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

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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, …

Science advances, Vol.10(8), eadk9004

02/23/2024

DOI: 10.1126/sciadv.adk9004

PMCID: PMC10889430

PMID: 38394202

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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.

Details

Title: Subtitle: An orally active entry inhibitor of influenza A viruses protects mice and synergizes with oseltamivir and baloxavir marboxil
Creators: Irina Gaisina - Chicago BioSolutions Inc., Chicago, IL 60612, USA
Ping Li - Shandong University of Traditional Chinese Medicine
Ruikun Du - Shandong University of Traditional Chinese Medicine
Qinghua Cui - Shandong University of Traditional Chinese Medicine
Meiyue Dong - Shandong University of Traditional Chinese Medicine
Chengcheng Zhang - Shandong University of Traditional Chinese Medicine
Balaji Manicassamy - Department of Microbiology and Immunology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Michael Caffrey - University of Illinois Chicago
Terry Moore - University of Illinois Chicago
Laura Cooper - University of Illinois Chicago
Lijun Rong - University of Illinois Chicago
Resource Type: Journal article
Publication Details: Science advances, Vol.10(8), eadk9004
DOI: 10.1126/sciadv.adk9004
PMID: 38394202
PMCID: PMC10889430
NLM abbreviation: Sci Adv
eISSN: 2375-2548
Language: English
Date published: 02/23/2024
Academic Unit: Microbiology and Immunology
Record Identifier: 9984560488802771

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