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TitleA human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 6335, Year 2023
Publish dateOct 10, 2023
AuthorsAndrew J Charnesky / Julia E Faust / Hyunwook Lee / Rama Devudu Puligedda / Daniel J Goetschius / Nadia M DiNunno / Vaskar Thapa / Carol M Bator / Sung Hyun Joseph Cho / Rahnuma Wahid / Kutub Mahmood / Scott Dessain / Konstantin M Chumakov / Amy Rosenfeld / Susan L Hafenstein /
PubMed AbstractGlobal eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 ...Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.
External linksNat Commun / PubMed:37816742 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.15 Å
Structure data

EMDB-27943, PDB-8e8l:
9H2 Fab-poliovirus 1 complex
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-27947, PDB-8e8r:
9H2 Fab-Sabin poliovirus 3 complex
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-27948, PDB-8e8s:
9H2 Fab-poliovirus 2 complex
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-27949, PDB-8e8x:
9H2 Fab-Sabin poliovirus 3 complex
Method: EM (single particle) / Resolution: 2.91 Å

EMDB-27950, PDB-8e8y:
9H2 Fab-Sabin poliovirus 2 complex
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-27951, PDB-8e8z:
9H2 Fab-Sabin poliovirus 1 complex
Method: EM (single particle) / Resolution: 3.15 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • human poliovirus 1 mahoney
  • homo sapiens (human)
  • human poliovirus 3 strain sabin
  • poliovirus 2
  • human poliovirus 2 strain sabin
  • human poliovirus 1 strain sabin
KeywordsVIRUS/IMMUNE SYSTEM / Complex / Fab / poliovirus / neutralizing / VIRUS-IMMUNE SYSTEM complex

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