Discovery and Advancement of Chikungunya virus inhibitors

DESCRIPTION provided by applicant Novel inhibitors of Chikungunya virus CHIKV are urgently needed to address the alarming spread of this pathogen across the Americas The objective of this Phase I SBIR feasibility study is to identify up to drug like compound lead series that specifically and selectively inhibit CHIKV replication in cell culture To this end we have developed and validated a high throughput screening assay that is suitable for compound screening against active CHIKV replication in cell culture We will conduct a high throughput anti CHIKV screening campaign of a library of over compounds with optimal drug like properties Quality hits that emerge from this campaign will be profiled for potency selectivity spectrum of activity against CHIKV and related alphaviruses and mechanism of action The most interesting of the compound series will undergo medicinal chemistry hit to lead efforts to explore structure activity relationships SAR Early assessment of the oral bioavailable of representative compounds from each series will be undertaken Success will trigger the submission of a Phase II SBIR grant that will drive chemical optimization of the series to andquot Candidate Selection for Pre developmentandquot Phase II will include Proof of Concept testing in animal models of CHIKV disease in the laboratory of Dr Weaver at UTMB The work described herein is expected to lead to the identification of one or more urgently needed inhibitor series that target Chikungunya virus PUBLIC HEALTH RELEVANCE A Chikungunya virus CHIKV epidemic is raging across the Americas Morbidity associated with CHIKV infection includes severe debilitating arthralgia joint pain that can persist for years There are no antiviral agents or vaccines approved for CHIKV treatment or prevention Here we propose to identify a new lead series of CHIKV inhibitors utilizing a sensitive and reproducible virus replication based high throughput screening system developed at VenatoRx