Designer drugs to inhibit hepatitis A virus

Structure-based drug design revealed that a compound previously investigated for the treatment of head-and-neck cancer could function as a lead compound for the development of drugs to treat hepatitis A virus infection, according to a study publishing April 30 in the open-access journal PLOS Biology by Dan Su of Sichuan University, Zihe Rao of Tsinghua University, Xiangxi Wang of the Chinese Academy of Sciences, and colleagues.

Hepatitis A caused by is a picornavirus that infects approximately 1.5 million people annually and continues to cause substantial mortality. Although there are effective vaccines, antivirals against hepatitis A infection are still required during outbreaks, and to date there are no licensed therapeutic drugs. The authors hypothesized that better knowledge of how neutralizing antibodies naturally defend cells from hepatitis A infection might facilitate the development of hepatitis A-targeting antiviral drugs.

In the new study, the authors report four potent hepatitis A virus-specific neutralizing antibodies, together with their previously reported one, that efficiently inhibit hepatitis A virus infection by blocking the virus’s ability to attach to the host cell. The authors used high-resolution cryogenic electron microscopy to visualize structures of hepatitis A virus bound to the antibodies. This gave them insights into the structural basis of how the antibodies neutralize the virus, informing the rational design of highly potent inhibitors.

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