Optimization of a broad-spectrum Ebolavirus cell entry inhibitor chemical series as a countermeasure for parental and aerosol routes of infection

Ebolavirus species including Zaire (EBOV), Sudan (SUDV) and Bundibugyo (BDBV) are responsible for severe hemorrhagic fever outbreaks with high case fatalities in Africa [1,2]. Outbreaks of EBOV in the Democratic Republic of the Congo (DRC) as well as the 2014-2016 outbreak in West Africa highlight the danger that these zoonotic viruses pose through mucosal routes of infection and secondary human to human transmission. Weaponized pathogens present an additional threat to the health protection of the warfighter and first-generation prophylactic and therapeutic medical countermeasures (MCMs) may prove inadequate in biodefense settings. Ebolaviruses present both potential public health and bioweapons threats and the development of second-generation therapeutics targeting novel mechanisms for antiviral activity may help to provide auxiliary means of protection. The objective of this proposal is to demonstrate feasibility of generating a dual use broad-spectrum small molecule ebolavirus therapeutic.