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TitleA unified route for flavivirus structures uncovers essential pocket factors conserved across pathogenic viruses.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 3266, Year 2021
Publish dateJun 1, 2021
AuthorsJoshua M Hardy / Natalee D Newton / Naphak Modhiran / Connor A P Scott / Hariprasad Venugopal / Laura J Vet / Paul R Young / Roy A Hall / Jody Hobson-Peters / Fasséli Coulibaly / Daniel Watterson /
PubMed AbstractThe epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden of viruses such as dengue. Structural analysis is key to understand and combat ...The epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden of viruses such as dengue. Structural analysis is key to understand and combat these pathogens. Here, we present a chimeric platform based on an insect-specific flavivirus for the safe and rapid structural analysis of pathogenic viruses. We use this approach to resolve the architecture of two neurotropic viruses and a structure of dengue virus at 2.5  Å, the highest resolution for an enveloped virion. These reconstructions allow improved modelling of the stem region of the envelope protein, revealing two lipid-like ligands within highly conserved pockets. We show that these sites are essential for viral growth and important for viral maturation. These findings define a hallmark of flavivirus virions and a potential target for broad-spectrum antivirals and vaccine design. We anticipate the chimeric platform to be widely applicable for investigating flavivirus biology.
External linksNat Commun / PubMed:34075032 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.7 Å
Structure data

23042

7kv8

EMDB-23042, PDB-7kv8:
Chimeric flavivirus between Binjari virus and Dengue virus serotype-2
Method: EM (single particle) / Resolution: 2.5 Å

23043

7kv9

EMDB-23043, PDB-7kv9:
Chimeric flavivirus between Binjari virus and West Nile (Kunjin) virus
Method: EM (single particle) / Resolution: 2.9 Å

23044

7kva

EMDB-23044, PDB-7kva:
Structure of West Nile virus (Kunjin)
Method: EM (single particle) / Resolution: 3.1 Å

23045

7kvb

EMDB-23045, PDB-7kvb:
Chimeric flavivirus between Binjari virus and Murray Valley encephalitis virus
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-1Q0:
(2S,3R,4Z)-3-hydroxy-2-[(9E)-octadec-9-enoylamino]octadec-4-en-1-yl dihydrogen phosphate

ChemComp-HOH:
WATER

Source
  • dengue virus 2
  • kunjin virus
  • murray valley encephalitis virus
KeywordsVIRUS / Flavivirus / glycoprotein / entry / fusion / Chimera / West Nile

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