In Vitro and In Vivo Models for Drug Development Against Two Hemorrhagic Hareavirales: Rift Valley Fever and Crimean Congo Hemorrhagic Fever Viruses

Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) are designated by the World Health Organization as priority pathogens due to their epidemic potential, zoonotic transmission, and the absence of licensed therapeutics or vaccines. The development of effective antivirals critically relies on robust in vitro and in vivo models; however, progress is limited by the requirement for high-containment facilities. In this review, we provide a comprehensive overview of the experimental models currently available for RVFV and CCHFV, ranging from cell-based assays to animal models, and discuss their respective advantages, limitations, and translational relevance. We further highlight strategies allowing for BSL-2 experimentations, thereby expanding research accessibility, and accelerating the development of countermeasures against these high-priority pathogens.