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From Proteopedia
CCHFV GP38 bound to ADI-46152 and ADI-58048 Fabs
Structural highlights
FunctionGP_CCHFI Glycoprotein C and glycoprotein N interact with each other and are present at the surface of the virion. They are able to attach the virion to host cell receptors. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Also promotes fusion of viral membrane with host endosomal membrane after endocytosis of the virion (By similarity).[1] Publication Abstract from PubMedCrimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics. Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.,Shin OS, Monticelli SR, Hjorth CK, Hornet V, Doyle M, Abelson D, Kuehne AI, Wang A, Bakken RR, Mishra AK, Middlecamp M, Champney E, Stuart L, Maurer DP, Li J, Berrigan J, Barajas J, Balinandi S, Lutwama JJ, Lobel L, Zeitlin L, Walker LM, Dye JM, Chandran K, Herbert AS, Pauli NT, McLellan JS Cell Rep. 2024 Jul 12;43(7):114502. doi: 10.1016/j.celrep.2024.114502. PMID:39002130[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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