ABSTRACT
Zika virus, transmitted primarily by mosquitos, could become endemic in the tropical and subtropical regions including the southern states and territories of the United States. It could cause catastrophic consequences to the public health, such as microcephaly (small brain/head) of newborns. However, there are no antiviral drugs or vaccines for Zika infection. Zika virus protease (ZVpro) is a viral protein that is essential for viral replication. ZVpro is therefore a drug target. The overall goal of this project is to use a combination of rational inhibitor design, medicinal chemistry, X-ray crystallography and antiviral activity testing to discover small-molecule inhibitors of ZVpro, which are potential drug candidates for Zika infection. During the second funding period, although the overall progress has been delayed due to the COVID-19 pandemic, our activities and results have been satisfactory, showing our potent ZVpro inhibitors are non-cytotoxic and have strong in vitro and in vivo anti-ZIKV activity. We will perform the experiments in accordance with the approved SOW to achieve the goals of the project in the next funding period.