Novel antiviral based on crosslinking Marburgvirus nucleoprotein

Therapeutics are scarce for several important viral groups and the situation is further confounded by the ability of viruses to rapidly mutate and evolve resistance to drugs. Filoviruses, such as Marburg and Ebola virus, are no exception to this. Researchers have shown viral mutations that lead to the virus being able to evade detection by neutralizing antibodies and evade host immunity. Dr. Hayhurst’s approach is to target an internal antigen, which is a molecule not under selective pressure to evolve thereby making a resistant proof therapeutic. We have a panel of llama single domain antibodies that bind to a region of Marburg virus nucleoprotein that has shown no mutations since it emerged in 1967. We aim to engineer one of these antibodies to crosslink nucleoprotein molecules within the cell to “confuse” the viral replication machinery, essentially jamming it and reducing the yield of progeny virus. Because the nanobodies are so small and easily engineered it is conceivable that the approach can be combined with our anti-Ebola nucleoprotein antibodies which cross-react among 5 different Ebola species to form a broad spectrum anti-Filovirus drug. When successful, and with the appropriate antibodies, it is possible to extend this strategy to countering other viruses.