Abstract
Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. However, the emergence of resistant strains remains a constant threat and consideration. Antivirals targeting the hemagglutinin protein are relatively new and have yet to gain global use but are proving to be effective additions to the antiviral repertoire, with a relatively high threshold for the emergence of resistance. Here we review antiviral drugs, both approved for clinical use and under investigation, that target the influenza virus hemagglutinin and neuraminidase proteins, focusing on their mechanisms of action and the emergence of resistance to them.
Highlights
Vaccination remains one of the central public health interventions to combat seasonal influenza
Baloxavir marboxil is under license in Japan, the United States of America (USA), Hong Kong, Australia and Europe, whilst favipiravir is licensed for limited use in Japan and under Phase III clinical trial in the USA and Europe [3]
The focus of this review is antiviral resistance to HA and NA inhibitors from the perspectives of epidemiology, molecular virology and pharmacology with the goal of providing a review of the impact, developments and challenges associated with antiviral drug resistance in influenza viruses
Summary
Vaccination remains one of the central public health interventions to combat seasonal influenza. The first class of anti-influenza drug to be approved for use were the adamantanes, which block the M2 ion channel on the surface of the virion [1] This activity decreases ion flow and endosome acidification, inhibiting the low pH-induced fusion of the viral membrane with the endosome. Polymerase and nucleoprotein inhibitors that target the replication machinery of influenza viruses have been developed Two of these drugs, baloxavir marboxil and favipiravir, have reached the market but are not commonly used at present. The surface glycoproteins of influenza A and B viruses, consisting of the hemagglutinin (HA) and neuraminidase (NA) proteins, are the most exposed proteins of influenza virus This makes them prominent targets for interventions such as vaccines, antibodies and antivirals. The focus of this review is antiviral resistance to HA and NA inhibitors from the perspectives of epidemiology, molecular virology and pharmacology with the goal of providing a review of the impact, developments and challenges associated with antiviral drug resistance in influenza viruses
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