9zmq | pdb_00009zmq
X-ray crystallographic structure of CCHFV nucleocapsid-protein Afg09-2990 bound with 9D5-Fab.
Structural highlights
FunctionQ8JPR4_9VIRU Binds dsRNA and ssRNA and probably participates in the packaging of viral genome. In the dsRNA binding mode, the nucleocapsid protein specifically binds to the vRNA panhandle secondary structure formed at the termini of viral genome. Does not discriminate between viral and nonviral RNAs through ssRNA binding mode. Displays dsDNA endonuclease activity that is sequence non-specific.[ARBA:ARBA00046210] Publication Abstract from PubMedCrimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne virus endemic to Africa, Asia, and expanding regions within Europe. With mortality rates approaching 40%, rising incidence, and no currently approved countermeasures, CCHFV is recognized as a priority public health threat. CCHFV nucleocapsid protein (NP) has long been a key target for diagnostics. Recently, NP-specific humoral responses have also been correlated with protection conferred by protective vaccines candidates. Additionally, the first non-neutralizing monoclonal antibody (mAb) 9D5 demonstrated protective efficacy against CCHFV challenge, underscoring NP as a viable antiviral target. Here, nine anti-NP mAb were utilized to identify four antigenic sites on NP as well as localize these sites to the head or stalk domains. These mAb also revealed variable levels of in vivo protection, independent from whether the epitope site is located in the head or stalk regions. Additionally, three X-ray crystallography structures were obtained that included CCHFV NP from strain Afg09-2990 in complex with the most potent mAb (9D5). This, along with additional structures of two unbound NPs, revealed structural elements critical for mAb-9D5 broad-spectrum protective characteristics. These findings provide a path towards the rapid identification of broadly protective anti-NP mAb countermeasures. Structural and mechanistic insights into protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus nucleocapsid protein.,Moresco V, Garrison AR, Edmundo CA, Fitzpatrick CJ, Karaaslan E, Olschner SP, Ricks KM, Ogundare OT, Tadri L, Carey BD, Sajadi MM, Bergeron E, Golden JW, Pegan SD Nat Commun. 2026 Aug 21;17(1):9967. doi: 10.1038/s41467-026-76702-1. PMID:42754559[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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