Abstract
Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.
Highlights
Main Influenza A viruses (IAV) cause acute respiratory diseases in humans, birds, and other mammals, representing one of the major threats to public health
We described the functional and structural studies leading to the discovery of HA as a new anti-influenza target, and how structural information is facilitating the rational design of new IAV entry inhibitors targeting HA
Analyses of the H1-typed HA sequence variation from natural influenza virus isolates causing epidemics and study of the virus mutations induced by anti-influenza monoclonal antibodies, 5 antigenic sites were identified on H1-typed HA
Summary
Main Influenza A viruses (IAV) cause acute respiratory diseases in humans, birds, and other mammals, representing one of the major threats to public health. An unexpected human adaptation of an influenza subtype or strain rather than currently circulating influenza viruses may cause pandemic flu. The H5N1 type IAV, which infected 18 patients in Hong Kong and caused 6 death in 1997, is a potentially serious threat to human health in the near future because of its high mortality (about 60%) and potential human-to-human transmission. It is the only way to use antiinfluenza agents for treatment and prevention at the beginning of pandemic outbreak of a virulent influenza strain, which gives time for the development and widespread dissemination of an effective vaccine. Oseltamivir and zanamivir, were both approved in 1999 for treatment and prevention for acute uncomplicated flu caused by influenza A and B. Grey dots represent nodes; Blue dots represent 16 subtypes of influenza A virus HA proteins
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