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How Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets...

by Szu Hua Chen, M Todd Young, John P Gounley, Christopher B Stanley, Debsindhu Bhowmik
Publication Type
Conference Paper
Journal Name
IEEE International Conference on Big Data
Book Title
2021 IEEE International Conference on Big Data (Big Data)
Publication Date
Page Numbers
4333 to 4341
Publisher Location
New Jersey, United States of America
Conference Name
IEEE International Conference on Big Data (IEEE BigData 2021)
Conference Location
Virtual, Tennessee, United States of America
Conference Sponsor
seagate, IEEE
Conference Date

The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with all-atom molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.