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

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.