Cathepsin B Inhibitors as Therapeutics for Ebola Infection

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 DESCRIPTION (provided by applicant): Ebola virus (EBOV) of the filovirus family is an enveloped, single-stranded RNA virus that causes severe hemorrhagic fever in multiple mammals including humans and non-human primates. The recent 2013-2014 outbreak of EBOV in West Africa has resulted in the deaths of nearly 40% of infected patients to date, spreading throughout West Africa and internationally to the United States and Spain via travelers. Therefore, it is essential to understand how this virus invades its hosts and causes disease, to spur approaches to treatment and prevention. Because entry into host cells is the first step in the viral life cycle, this area offers a major target for treatment and prevention. Importantly, ithas been demonstrated that EBOV requires the activity of human Cathepsin B (CatB) for sequential processing of its glycoprotein GP1. The fact that EBOV utilizes this key human protease, CatB, for entry offers an opportunity to develop anti-EBOV inhibitor drugs. We aim to generate potent, specific inhibitors for CatB via exploration of the prime side -helical binding pocket that resuts in inhibition of EBOV infection in live cell assays.