Crimean-Congo Hemorrhagic Fever virus (CCHFV)

Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a highly pathogenic, tick-borne virus in the Orthonairovirus genus, characterized by a tripartite, negative-sense RNA genome [9, 10]. It is the causative agent of Crimean-Congo Hemorrhagic Fever (CCHF), a severe disease with a case fatality rate reaching up to 40%, distributed across Africa, Asia, Southeastern Europe, and the Middle East [2, 12]. The virus genome consists of Small (S), Medium (M), and Large (L) segments that encode key structural and functional proteins, including the nucleocapsid protein, envelope glycoproteins (Gn and Gc), and a large protein containing both an RNA-dependent RNA polymerase (RdRp) and an ovarian tumor-like (OTU) protease [9, 11]. CCHFV utilizes its OTU domain to deubiquitinate host proteins, effectively evading the innate immune system, while its glycoproteins mediate entry through clathrin-dependent endocytosis [2, 19]. There are currently no FDA-approved vaccines or specific antivirals for CCHF; ribavirin is often used under WHO recommendations despite conflicting evidence regarding its clinical efficacy [6, 10]. Experimental strategies are now exploring RdRp inhibitors like favipiravir, viral RNA structure stabilizers like cepharanthine, and host-directed therapies targeting metabolic pathways used during viral replication [4, 5, 16].

Other names

Crimean-Congo hemorrhagic fever orthonairovirusCCHF virusCongo virusOrthonairovirus flavicolle

RNA-dependent RNA polymerase (RdRp) inhibition; viral RNA G-quadruplex structure stabilization; inhibition of viral entry and clathrin-mediated endocytosis; deubiquitination and de-ISGylation inhibition via the OTU protease domain; inhibition of host glycolysis and glutaminolysis pathways.