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Pathway Description
Ansuvimab Action Pathway
Homo sapiens
Drug Action Pathway
Ansuvimab (formerly mAb114) is a monoclonal IgG1 antibody derived from a survivor of the 1995 kikwit EBOV (Ebola virus) outbreak. It is directed against the GP1,2 surface glycoprotein of Zaire ebolavirus .It is used for the treatment of Zaire ebolavirus infection in adult and pediatric patients. This drug has been approved by the FDA in 2020. The DP1,2 glycoproteins of EBOV are involved in the the host cell entry and the subsequent viral espape into the cytoplasm. Usually, those glycoproteins bind to various host receptors (lectins, asialoglycoprotein receptor, TIM1), but with the drug, they are blocked. Ansuvimab binds over a region encompassing both the glycan cap and GP1 core, although the glycan cap isnot important in the binding. Also, studies have shown that the GP1 core is important for the GPCL interaction with NPC1 and thus this drug blocks NPC1-GP interactions (endolysosome escape). The drug protect against the entry of the virus in the host cells. Ansuvimab is available as an intravenous injection.
References
Ansuvimab Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Gaudinski MR, Coates EE, Novik L, Widge A, Houser KV, Burch E, Holman LA, Gordon IJ, Chen GL, Carter C, Nason M, Sitar S, Yamshchikov G, Berkowitz N, Andrews C, Vazquez S, Laurencot C, Misasi J, Arnold F, Carlton K, Lawlor H, Gall J, Bailer RT, McDermott A, Capparelli E, Koup RA, Mascola JR, Graham BS, Sullivan NJ, Ledgerwood JE: Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study. Lancet. 2019 Mar 2;393(10174):889-898. doi: 10.1016/S0140-6736(19)30036-4. Epub 2019 Jan 24.
Pubmed: 30686586
Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ: Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.
Pubmed: 26917593
Hoenen T, Groseth A, Feldmann H: Therapeutic strategies to target the Ebola virus life cycle. Nat Rev Microbiol. 2019 Oct;17(10):593-606. doi: 10.1038/s41579-019-0233-2. Epub 2019 Jul 24.
Pubmed: 31341272
Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS: Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.
Pubmed: 26917592
Jacob ST, Crozier I, Fischer WA 2nd, Hewlett A, Kraft CS, Vega MA, Soka MJ, Wahl V, Griffiths A, Bollinger L, Kuhn JH: Ebola virus disease. Nat Rev Dis Primers. 2020 Feb 20;6(1):13. doi: 10.1038/s41572-020-0147-3.
Pubmed: 32080199
Saphire EO, Schendel SL, Gunn BM, Milligan JC, Alter G: Antibody-mediated protection against Ebola virus. Nat Immunol. 2018 Nov;19(11):1169-1178. doi: 10.1038/s41590-018-0233-9. Epub 2018 Oct 17.
Pubmed: 30333617
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