Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations

Mert Gur; Elhan Taka; Sema Zeynep Yilmaz; Ceren Kilinc; Umut Aktas; Mert Golcuk

Recognition of host cell and entry of the virus are the most critical steps determining the pathogenesis and viral infectivity in viral infections (Gallagher and Buchmeier 2001) . Host cell recognition and fusion between host cell and viral membranes is provided by large trimeric spike (S) glycoproteins located on the CoV membrane ( Fig. 1) (Belouzard et al. 2012 ). These S proteins interact with the human epithelial and respiratory cells via the angiotensin-converting enzyme 2 (ACE2) receptors of the host cells (Letko et al. 2020 , Wrapp, Wang et al. 2020 . Upon receptor binding and proteolytic cleavage, large-scale conformational changes in S protein structure occur and S protein interaction with the host cell membrane takes place facilitating the fusion process. Due to their critical role in the entry of coronaviruses into host cells, SARS-CoV-2 S proteins have emerged as a popular and promising therapeutic target. In the current study, structure and dynamics of the SARS-CoV-2 S protein is investigated via allatom molecular dynamics (MD) simulations to provide critical atomic level insight into the conformational transition mechanism of S protein from a receptor inaccessible closed to an accessible open state, which in turn has the potential to strongly benefit development of therapeutic strategies for COVID-19.