Development of Novel Arenavirus Inhibitors into drug like substances
Arenaviruses are highly infectious and include viruses such as Lassa virus, Junin virus, Machupo virus. Lassa fever alone causes 100,000 to 300,000 infections per year with approximately 5,000 deaths. Strikingly, this is more than four to ten times the number of infections per year than all Ebola virus cases ever recorded (~28,000). Yet, the pace of research to develop antivirals against Arenaviruses is extremely slow. Except for Ribavirin, no FDA approved drugs or vaccines are available to treat these viruses. Ribavirin has several significant side effects and is only successful when administered early during infection. We have screened a 350,000 molecule library for inhibitors of Lassa virus entry and identified 5 novel inhibitor compounds. These compounds obstruct Lassa virus infection in a human cell line. Dr. Anantpadma’s project is an effort to modify these compounds to have drug like properties. Once modified into drugs, the mechanisms of action of compounds will be studied. This data is necessary for FDA approval and testing in humans. Some of our drugs may be able to inhibit other dangerous Arenaviruses such as Junin and Machupo as well. The findings will therefore have a large impact on the fields of anti-Arenaviral research and disease treatment.