Novel inhibitors of Zika virus (ZIKV) are urgently needed to prevent the occurrence of virus-induced microcephaly and Guillain-Barr syndrome. The objective of this Phase I SBIR feasibility study is to identify drug-like compounds that specifically inhibit ZIKV replication. During the course of this Phase I funding period, we will execute hit finding campaign against a library of 100,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven hit-to-lead to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or more novel lead series which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against the available ZIKV strains and minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection.
Novel therapies with potent and selective activity against Zika virus (ZIKV) are urgently needed for the prevention of ZIKV-associated diseases including microcepahly and Guillain-Barr syndrome. We propose to execute an innovative high throughput screening campaign. This screen is expected to yield novel compounds targeting ZIKV replication that will serve as starting points for medicinal chemistry hit-to-lead efforts. If successful, we will deliver one or more new lead series targeting ZIKV infection.