Cobra venom factor: Structure, function, and humanization for therapeutic complement depletion.
Cobra venom factor (CVF) is the complement-activating protein in cobra venom. This manuscript reviews the structure and function of CVF, how it interacts with the complement system, the structural and functional homology to complement component C3, and the use of CVF as an experimental tool to decomplement laboratory animals to study the functions of complement in host defense and immune response as well as in the pathogenesis of diseases. This manuscript also reviews the recent progress in using the homology between CVF and C3 to study C3 structure and function, and to develop human C3 derivatives with the complement-depleting function of CVF. These human C3 derivatives represent humanized CVF, and are a conceptually different concept for pharmacological intervention of the complement system, therapeutic complement depletion. The use of humanized CVF for therapeutic complement depletion in several pre-clinical models of human diseases is also reviewed.
Vogel
Carl-Wilhelm
CW
Cancer Research Center of Hawaii, University of Hawaii at Manoa, 1236 Lauhala Street, Honolulu, HI 96813, USA. cvogel@crch.hawaii.edu
Fritzinger
David C
DC
D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000473:pathology; D003176:Complement C3 / Q000737:chemistry* / Q000502:physiology; D051056:Complement Inactivating Agents / Q000737:chemistry* / Q000276:immunology; D004546:Elapid Venoms / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D017386:Sequence Homology, Amino Acid
D003176:Complement C3; D051056:Complement Inactivating Agents; D004546:Elapid Venoms; D011993:Recombinant Fusion Proteins; C016310:cobra venom factor