Cathepsin B Inhibitors as Therapeutics for Ebola Infection

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 outbreak of EBOV in West Africa has resulted in the deaths of nearly 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 GP 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 PUBLIC HEALTH RELEVANCE Ebola virus causes severe hemorrhagic fever in multiple mammals including humans and non human primates The recent outbreak of Ebola in West Africa has resulted in the deaths of nearly of infected patients to date spreading throughout West Africa and internationally to the United States and Spain via travelers There are currently no FDA approved drugs available for treatment of Ebola infection thus the development of therapeutic agents to treat this infection is an essential unmet medical need Ebola virus requires a human enzyme for the completion of the life cycle We aim to generate potent specific lead inhibitors for this enzyme to develop therapeutics for both Ebola viral infections in people