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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/Q8JUA9_9RHAB Q8JUA9_9RHAB] | [https://www.uniprot.org/uniprot/Q8JUA9_9RHAB Q8JUA9_9RHAB] | ||
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== Publication Abstract from PubMed == | |||
Rabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, the development of clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes the administration of Rabies immunoglobulin (RIG). However, the high cost and limited availability of serum-derived RIG severely hamper its wide use in resource-limited countries. A safe low-cost alternative is provided by using broadly neutralizing monoclonal antibodies (bnAbs). Here we report the X-ray structure of one of the most potent and most broadly reactive human bnAbs, RVC20, in complex with its target domain III of the RABV glycoprotein (G). The structure reveals that the RVC20 binding determinants reside in a highly conserved surface of G, rationalizing its broad reactivity. We further show that RVC20 blocks the acid-induced conformational change required for membrane fusion. Our results may guide the future development of direct antiviral small molecules for Rabies treatment. | |||
Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein.,Hellert J, Buchrieser J, Larrous F, Minola A, de Melo GD, Soriaga L, England P, Haouz A, Telenti A, Schwartz O, Corti D, Bourhy H, Rey FA Nat Commun. 2020 Jan 30;11(1):596. doi: 10.1038/s41467-020-14398-7. PMID:32001700<ref>PMID:32001700</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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==See Also== | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> |
Latest revision as of 13:30, 23 October 2024
Rabies virus glycoprotein PH domain in complex with the scFv fragment of broadly neutralizing human antibody RVC20Rabies virus glycoprotein PH domain in complex with the scFv fragment of broadly neutralizing human antibody RVC20
Structural highlights
FunctionPublication Abstract from PubMedRabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, the development of clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes the administration of Rabies immunoglobulin (RIG). However, the high cost and limited availability of serum-derived RIG severely hamper its wide use in resource-limited countries. A safe low-cost alternative is provided by using broadly neutralizing monoclonal antibodies (bnAbs). Here we report the X-ray structure of one of the most potent and most broadly reactive human bnAbs, RVC20, in complex with its target domain III of the RABV glycoprotein (G). The structure reveals that the RVC20 binding determinants reside in a highly conserved surface of G, rationalizing its broad reactivity. We further show that RVC20 blocks the acid-induced conformational change required for membrane fusion. Our results may guide the future development of direct antiviral small molecules for Rabies treatment. Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein.,Hellert J, Buchrieser J, Larrous F, Minola A, de Melo GD, Soriaga L, England P, Haouz A, Telenti A, Schwartz O, Corti D, Bourhy H, Rey FA Nat Commun. 2020 Jan 30;11(1):596. doi: 10.1038/s41467-020-14398-7. PMID:32001700[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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