TY - JOUR
T1 - Aryl Sulfonamide Inhibits Entry and Replication of Diverse Influenza Viruses via the Hemagglutinin Protein
AU - White, Kris
AU - Esparza, Matthew
AU - Liang, Jue
AU - Bhat, Prasanna
AU - Naidoo, Jacinth
AU - McGovern, Briana L.
AU - Williams, Michael A.P.
AU - Alabi, Busola R.
AU - Shay, Jerry
AU - Niederstrasser, Hanspeter
AU - Posner, Bruce
AU - García-Sastre, Adolfo
AU - Ready, Joseph
AU - Fontoura, Beatriz M.A.
N1 - Funding Information:
This work was supported by NIH Grants R33 AI119304-01 (to B.M.A.F. and A.G.-S.), R01AI125524-01 (to B.M.A.F. and A.G.-S.), and R01 AI154635, and the Welch Foundation (I-1612, to J.R.). This work was also partly supported by the Center for Research in Influenza Pathogenesis (CRIP), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C) to A.G.-S. We thank Richard Cadagan for excellent technical assistance.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/8/12
Y1 - 2021/8/12
N2 - 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.
AB - 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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U2 - 10.1021/acs.jmedchem.1c00304
DO - 10.1021/acs.jmedchem.1c00304
M3 - Article
C2 - 34260245
AN - SCOPUS:85111181514
VL - 64
SP - 10951
EP - 10966
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 15
ER -