Cap-dependent endonuclease inhibitors (CENis) - NHRC

Summary (Newest Update)

Background The Naval Medical Research Command is seeking to advance the preclinical development of Cap-dependent endonuclease inhibitors (CENi), a class of small molecules that have shown promise as broad-spectrum antiviral therapeutics. This initiative addresses the critical need for effective antiviral drugs in response to emerging and re-emerging viral infections, particularly those caused by bunyaviruses and other RNA viruses, which pose significant threats to national security and public health. The project aims to establish a robust therapeutic platform capable of rapid deployment against various viral pathogens. Work Details The scope of this project encompasses all necessary activities to select lead CENi candidates, including: 1. In vitro and in vivo efficacy studies of existing CENi compounds against arenaviruses. 2. Identification and characterization of new CENi compounds with potential broad-spectrum antiviral activity against other bunyaviruses. 3. Characterization, optimization, and evaluation of in vivo efficacy for lead CENi compounds targeting bunyaviruses. Specific tasks include: - Demonstrating broad-spectrum activity of anti-arenavirus CENi compounds through in vitro screening assays using positive controls like ribavirin against Lassa virus (LASV), Lujo virus (LUJV), and Crimean-Congo hemorrhagic fever virus (CCHFV). - Providing the Naval Medical Research Center (NMRC) with 50 anti-arenavirus CENi compounds for further screening. - Conducting in vitro efficacy assessments of these compounds against LUJV and CCHFV. - Screening an additional 50 new CENi compounds previously shown to have antiviral activity against surrogate BSL-2 bunyaviruses for efficacy against LASV, LUJV, and CCHFV. - Obtaining necessary approvals for animal studies and conducting in vivo efficacy studies for three lead CENi compounds against LASV, LUJV, and CCHFV. - Developing a detailed Project Management Plan (PMP) and participating in monthly progress meetings. Period of Performance The contract will be performed over a period of 36 months. Place of Performance The work will be conducted at the University of Texas Medical Branch.