Antiviral Drug Discovery

We are interested in finding new potential drugs for influenza and other acute viral diseases, particularly those that currently lack any approved therapeutics. Traditionally antiviral drugs have been designed to target viral proteins but the development of resistance is a common problem. Viruses (particularly RNA viruses) encode a limited number of proteins and therefore they must rely on many host cell functions to complete their replication cycles. Therefore an alternative strategy would be to direct the drug at one of these essential host factors. The advantages of this are that the virus is far less likely to develop resistance and these drugs should also be effective against viruses that are already resistant to the current antivirals. Furthermore, as the dependence on cellular pathways is often a conserved feature of viral replication strategies it may be possible to find a single drug that is broadly effective against several viruses. Towards this goal, we are exploring the host requirements for efficient influenza virus replication to identify new potential drug targets. We are also screening libraries of small molecules using novel reporter assays for the identification of compounds with anti-influenza virus activity.

Virus Activation and Inhibition of Host Innate Immune Pathways
Another focus of the Shaw lab is the host antiviral response and specifically the mechanisms that viruses use to block this response. Viral proteins that can inhibit the host innate immune response are important determinants of viral pathogenicity. Understanding their mechanism of action and identifying compounds that prevent their activity will aid in the design of attenuated viruses for vaccine purposes or in the discovery of new antiviral drugs. One virus of particular interest to us is Nipah virus, with is a highly pathogenic, emerging paramyxovirus whose reservoir is the Pteropus fruit bat. Nipah virus encodes multiple proteins that inhibit the antiviral response in humans, and possible bats too, and our goal is to determine their mechanism(s) of action and their individual contributions to virus pathogenesis.