Existing Protease Inhibitors May Be Effective Against Chikungunya Virus, In-Silico-Guided Analysis Shows

Chikungunya virus (CHIKV) has caused two recent massive outbreaks sickening millions of people. Now, a team of researchers has shown that several existing compounds have potent activity against the critical CHIKV protease enzyme (see image). The research was published online on October 10, 2016 in Antimicrobial Agents and Chemotherapy. The article is titled “Design and Validation of Novel Chikungunya Virus Protease Inhibitors.” Chikungunya is a mosquito-borne, largely tropical disease that can cause fever, severe joint pain, headaches, nausea, and fatigue. "Here we exploited an approach that should, at least in theory, be a fast track for the development of compounds useful both for studies of the virus and as leads for development of antivirals," said corresponding author Andres Merits, Ph.D., Professor of Applied Virology, University of Tartu, Estonia. "The 3D-structures of conserved virus proteins are currently second--after the genome sequence--to be resolved for new, medically important viruses," said Dr. Merits. Theoretical chemists from among the Merits team used that information to predict, in silico, what already-existing chemicals might bind and inhibit the enzyme. Then, virologists on the team tested the identified compounds' abilities to inhibit the CHIKV protease activity in biochemical systems, and then in cultures of infected cells. Several of the compounds proved to be potent inhibitors of both RNA synthesis and virus replication. Interestingly, it appeared that some compounds used more than one mechanism to inhibit CHIKV replication. "While none of these compounds is ready to be used as an antiviral drug, they represent promising leads and excellent tools for follow-up studies," said Dr. Merits.
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