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

Autor:	White K; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Esparza M; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Liang J; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Bhat P; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Naidoo J; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., McGovern BL; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Williams MAP; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Alabi BR; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Shay J; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Niederstrasser H; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Posner B; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Ready J; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States., Fontoura BMA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2021 Aug 12; Vol. 64 (15), pp. 10951-10966. Date of Electronic Publication: 2021 Jul 14.
DOI:	10.1021/acs.jmedchem.1c00304
Abstrakt:	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.
Databáze:	MEDLINE
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