Title: Distinct structural feature of interactingmembrane domains towards viral fusogenecity - coronavirus andarenavirus
Speaker: JinwooLee, University of Maryland - College Park
Location: Conference Room (1116) of the Institute for Physical Science and Technology (IPST) Building
Hosted by: Jeffery Klauda
The pandemic caused by Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019(COVID-19), has emphasized the glaring necessity to study emerging viruses inpreparation for the next pandemic. One such virus is Lassa virus (LASV), anArenavirus endemic to West Africa that the World Health Organization (WHO) hasdeclared to require prioritized research due to its pandemic potential. Acritical step in the viral life cycle is membrane fusion, a process thatfacilitates the delivery of the viral genetic material into the target cell.The initiation of fusion of both viruses relies on a small domain within theviral glycoprotein, consisting of highly conserved, predominantly hydrophobicamino acids known as the fusion domain (FD). Intriguingly, both the Arenavirusand Coronavirus families contain the same structurally distinct FD with both anN-terminal fusion peptide (FP)and internal fusion loop (FL), twofusogenic motifs which has never before been observed in conjunction. Improvingour understanding of the underlying chemistry concerning the FD will fill majorknowledge gaps in the molecular mechanism of SARS-CoV-2 and LASV fusion and aidin future endeavors regarding the viruses. The goal is to understand thestructural and functional roles of multiple fusogenic regions within theSARS-CoV-2 and LASV FD and how environmental conditions impact this. We aim touse a cyclic approach to decipher how the FD initiates fusion that utilizessolution NMR to elucidate the structural rearrangement of the FD, followed bythermodynamic and kinetic investigation through ITC and a FRET-based fusionassay. This approach will permit us to investigate the structure-functionrelationship of the FD as a peptide and within the context of the viralglycoprotein, a novel approach that offers more physiological relevance to ourresults. Furthermore, the results will shed light on the molecular detailsintegral to membrane fusion, filling a significant knowledge gap regarding howthe structure-function of the SARS-CoV-2 and LASV FD contribute to thisprocess.