Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses

Entry
inhibitors are of particular importance in current efforts to develop
a new generation of anti-influenza virus drugs. Here we report certain
pentacyclic triterpenes exhibiting conserved structure features and
with in vitro anti-influenza virus activity comparable to and even
higher than that of oseltamivir. Mechanistic studies indicated that
these lead triterpenoids bind tightly to the viral envelope hemagglutinin
(HA), disrupting the interaction of HA with the sialic acid receptor
and thus the attachment of viruses to host cells. Docking studies
suggest that the binding pocket within HA for sialic acid receptor
potentially acts as a targeting domain, and this is supported by structure–activity
data, sialic acid competition studies, and broad anti-influenza spectrum
as well as less induction of drug resistance. Our study might establish
the importance of triterpenoids for development of entry inhibitors
of influenza viruses.