| Title |
Inhibition of SARS-CoV-2 viral RNA entry into the host cell by targeting the interaction of HR1 and HR2 domains of spike protein. |
| Researcher |
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Hossein Haghshenas (PHD student at Islamic Azad University of Shahrekord)
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| Abstract |
Recent studies have shown that the entry of the Coronaviruses into the host cells largely depends on the function of the spike glycoproteins. These glycoproteins can recognize ACE2 receptors on the surface of human lung alveolar epithelial cells in the lower respiratory tract. Spikes are trimeric fusion proteins and consist of two subunits S1 and S2. The S1 subunit binds to ACE2 receptors of the target cell via its receptor-binding domain (RBD), and subsequently, this interaction triggers an endosome formation in the host cell membrane. At this stage, cell membrane fusion between the host cell and virus takes place due to the conformational changes of the spike S2 subunit mediated by the interaction of two S2 heptad repeats domain named HR1 and HR2. Regard the critical role of spikes in mediating viral infection, and these glycoproteins can be considered as an essential target for viral infection drug design. In this study, we aim to perform a set of theoretical simulations using molecular dynamics techniques to investigate the mechanism of HR1-HR2 interaction and to design HR2-like inhibitors. We will study the molecular properties of HR1-HR2 interactions and their binding affinities, and then we will design a new HR2-like inhibitory peptide by modifying critical residues of the interaction site. |
