Mechanism of SARS-CoV2 Viral Fusion to Human Cells

Emad Tajkhorshid, University of Illinois at Urbana-Champaign

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Emad Tajkhorshid, Po-Chao Wen, Muyun Lihan, Nandan Haloi, Karanpal Kapoor, Ali Rasouli, Defne Gorgun, Tianle Chen

The pandemic caused by SARS-CoV2 continues to claim lives and impact nearly all aspects of our lives across the globe. Infection of human cells involves several molecular steps including binding of the virus to a specific human surface receptor and subsequent fusion of the viral membrane with the host cellular membrane, which allows for transport of the viral nucleic acid into the host cell.  One of the key molecular elements involved in this process is the “fusion peptide”, a highly conserved segment of the spike protein in coronaviruses that inserts into the host cell membrane and thereby initiates the fusion of the viral and host membranes.

Here, we aim at characterizing, at an atomic level, interaction of the fusion peptide with the host membrane using molecular dynamics simulations. We will investigate binding of the fusion peptide to lipid bilayers representing human cells and quantify the energetics of the process using free energy methods. We will take advantage of some of the novel models and techniques developed in our lab for studying membrane interaction of proteins and peptides, an area in which our lab has gained much experience over the past two decades. The results will shed light on a key step in SARS-CoV2 infection with potential application to designing inhibitors.

Given the conservation of the fusion peptides in coronaviruses in general, our results are applicable to infections caused by other members of this life-threatening family of pathogens.