IDENTIFICATION OF FLAVIVIRUS NUCLEOCAPSID CORE-ENVELOPE GLYCOPROTEIN INTERACTIONS - PROJECT SUMMARY/ABSTRAC…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_F31AI152453_075 · PURDUE UNIVERSITY · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_F31AI152453_075
- FAIN
- F31AI152453
- Recipient
- PURDUE UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.855
- Total obligated
- $68,704
- Period
- Jan 1, 2021 – Dec 31, 2022
- Fiscal year
- 2021
- Place of performance state
- IN
- Source file
- FY2021_All_Assistance_Full_20261006.zip
Description
IDENTIFICATION OF FLAVIVIRUS NUCLEOCAPSID CORE-ENVELOPE GLYCOPROTEIN INTERACTIONS - PROJECT SUMMARY/ABSTRACT FLAVIVIRUSES (A FAMILY OF OVER 90 KNOWN VIRUSES, INCLUDING ZIKA, DENGUE AND WEST NILE) ARE SIGNIFICANT HUMAN PATHOGENS AFFECTING 3.1 BILLION PEOPLE ANNUALLY, AND MOST OF THESE ENVELOPED VIRUSES DO NOT HAVE ANY VIABLE VACCINES OR ANTIVIRALS CAPABLE OF COMBATING THEIR SPREAD. THE PRIMARY OBJECTIVE OF CURRENT FLAVIVIRUS ANTIVIRAL DESIGN IS TO DISRUPT SPECIFIC MECHANISMS IN THE FLAVIVIRUS LIFE CYCLE THAT ARE KEY FOR VIRUS SURVIVAL, INCLUDING VIRUS ATTACHMENT TO THE HOST CELL, VIRAL ENDOCYTOSIS, GENOME UNCOATING, GENOME REPLICATION, AND VIRUS MATURATION THROUGH THE GOLGI. THESE POTENTIALLY DRUGGABLE MECHANISMS HAVE BEEN EXPLORED IN GREAT DETAIL BOTH WITHIN OUR LAB AND ELSEWHERE. HOWEVER, LITTLE IS KNOWN ABOUT THE ASSEMBLY MECHANISMS THAT DRIVE INFECTIOUS VIRUS PARTICLE FORMATION. BECAUSE OF THE HIGH STRUCTURAL HOMOLOGY AMONG ALL FLAVIVIRUSES, THE IDENTIFICATION OF ASSEMBLY MECHANISMS WILL PROVIDE UBIQUITOUS TARGETS FOR THERAPEUTIC INTERVENTION IN VIRUS PROLIFERATION. IN OTHER ENVELOPED VIRUS SYSTEMS, ASSEMBLY DEPENDS ON THE INTERACTION OF VIRUS CORE PROTEINS WITH LIPID MEMBRANES OR MEMBRANE BOUND GLYCOPROTEINS TO PRODUCE INFECTIOUS VIRUS PARTICLES. EXPLORATION VIA SINGLE PARTICLE CRYO-EM RECONSTRUCTION HAS SHOWN THAT THE NUCLEOCAPSID CORE (NC) OF IMMATURE ZIKA VIRUS, IS FOUND IN CLOSE PROXIMITY WITH THE ENVELOPE GLYCOPROTEINS ON THE INNER SIDE OF THE VIRUSâS LIPID BILAYER. DUE TO THIS CLOSE PROXIMITY, I HYPOTHESIZED THAT THE NC INTERACTS WITH THE ENVELOPE GLYCOPROTEINS DURING VIRUS ASSEMBLY. I FURTHER HYPOTHESIZED AND THAT THESE INTERACTIONS OCCUR BETWEEN THE CAPSID PROTEIN (CP) AND TRANSMEMBRANE HELICES OF THE PRECURSOR MEMBRANE (PRM) PROTEIN AND THE ENVELOPE (E) PROTEIN WHILE THE PARTICLE IS IN THE IMMATURE STATE. SINCE NO INFORMATION CURRENTLY EXISTS ON VIRUS ASSEMBLY RELYING ON CP-PRM/E INTERACTIONS, THESE INTERACTIONS HAVE THE POTENTIAL TO BE EXPLOITED AS