New Therapeutic Tactic for Flu and Other Respiratory Viruses
Proteases, enzymes that breakdown proteins, are important drug targets for many diseases, but targeting host cell proteases involved in virus entry has received little attention. In this collaborative project, Gary Whittaker, Microbiology and Immunology—with colleagues at John Hopkins and the University of Kentucky—proposes to develop therapeutics that can be used to treat multiple respiratory viruses by targeting the common set of host cell proteases critical for their activation.
Host cell proteases are tightly regulated, and the host has evolved highly specific inhibitors with a high affinity for their natural protease. The researchers utilize these natural inhibitors as an innovative host-targeted large molecule therapeutic approach for influenza and other enveloped respiratory viruses.
While the human genome has at least 500-600 proteases, there is a much smaller number of natural inhibitors. Therefore individual inhibitors act on multiple proteases within a given family, which is directly applicable to viral infection involving a subset of related proteases expressed in a given tissue. Whittaker’s approach has advantages over more traditional small molecule approach, which has a high degree of specificity but may not be active against the inbuilt redundancy of proteases need for virus entry in the respiratory tract. NIH Award Number: 1R21AI117300-01A1