Aryl Sulfonamide Inhibits Entry and Replication of Diverse Influenza Viruses via the Hemagglutinin Protein

  • J Med Chem. 2021 Aug 12;64(15):10951-10966. doi: 10.1021/acs.jmedchem.1c00304.
Kris White  1  2 ,  Matthew Esparza  3 ,  Jue Liang  4 ,  Prasanna Bhat  3 ,  Jacinth Naidoo  4 ,  Briana L McGovern  1  2 ,  Michael A P Williams  1  2 ,  Busola R Alabi  3 ,  Jerry Shay  3 ,  Hanspeter Niederstrasser  4 ,  Bruce Posner  4 ,  Adolfo García-Sastre  1  2  5  6 ,  Joseph Ready  4 ,  Beatriz M A Fontoura  3
Affiliations
  • 1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
  • 2. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
  • 3. Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
  • 4. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
  • 5. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
  • 6. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
PMID: 34260245 DOI: 10.1021/acs.jmedchem.1c00304
Abstract

Influenza viruses cause approximately half a million deaths every year worldwide. Vaccines are available but partially effective, and the number of Antiviral medications is limited. Thus, it is crucial to develop therapeutic strategies to counteract this major pathogen. Influenza viruses enter the host cell via their hemagglutinin (HA) proteins. The HA subtypes of influenza A virus are phylogenetically classified into groups 1 and 2. Here, we identified an inhibitor of the HA protein, a tertiary aryl sulfonamide, that prevents Influenza Virus entry and replication. This compound shows potent Antiviral activity against diverse H1N1, H5N1, and H3N2 influenza viruses encoding HA proteins from both groups 1 and 2. Synthesis of derivatives of this aryl sulfonamide identified moieties important for Antiviral activity. This compound may be considered as a lead for drug development with the intent to be used alone or in combination with Other influenza A virus antivirals to enhance pan-subtype efficacy.

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