Title:Inhibitors Targeting the Influenza Virus Hemagglutinin
Volume: 22
Issue: 11
Author(s): F. Li, C. Ma and J. Wang
Affiliation:
Keywords:
Adamantane, fusion inhibitors, hemagglutinin, influenza, membrane fusion.
Abstract: The annual flu season causes thousands of deaths and millions of hospitalizations, which
pose a great burden to global health and economy. Moreover, a flu pandemic arising from reassortment
viruses, such as H5N1 and H1N1, raises even greater concern due to the lack of effective vaccines at
the initial stage of flu outbreak. The influenza virus is the causative agent of flu infection. Currently
there are four drugs in use to combat influenza infection. Amantadine and rimantadine are M2 proton
channel blockers that inhibit virus uncoating; oseltamivir and zanamivir are neuraminidase (NA) inhibitors
that inhibit virus release. However, recent years have witnessed a drastic increase in instances of drug resistance,
and flu strains that are resistant to both classes of drugs have been reported. Thus, there is a pressing need to develop the
next generation of anti-influenza drugs. Among a handful of anti-influenza drug targets, the viral fusion protein hemagglutinin
(HA) is one of the most advanced. This review discusses the biological roles of HA during viral replication and highlights
peptide- and small molecule–based HA inhibitors, including recent computationally designed HA binders. The text
is organized into four sections based on the maturation stages of HA: inhibitors targeting the glycosylation of HA, the proteolytic
activation of HA, the attachment of HA to host cell receptors, and peptide- and small molecule–based inhibitors
targeting HA-mediated membrane fusion. Of particular interest are advances in the areas of developing dual inhibitors
targeting both HA and NA and broad-spectrum HA inhibitors targeting both groups of HAs.
