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Differential binding of SARS-CoV-2 Spike protein variants to its cognate receptor hACE2 using molecular modeling based binding analysis



Mirza Sarwar Baig, Enam Reyaz, Angamuthu Selvapandiyan & Anuja Krishnan*



Department of Molecular Medicine, School of Interdisciplinary Sciences & Technology, Jamia Hamdard, New Delhi - 110062, India





Article Type

Research Article



January 5, 2021; Revised February 24, 2020; Accepted February 27, 2020, Published February 28, 2021



The current emergence of novel coronavirus, SARS-CoV-2 and its ceaseless expansion worldwide has posed a global health emergency that has adversely affected the humans. With the entire world striving to understand the newly emerged virus, differences in morbidity and infection rate of SARS-CoV-2 have been observed across varied geographic areas, which have been ascribed to viral mutation and evolution over time. The homotrimeric Spike (S) glycoprotein on the viral envelope surface is responsible for binding, priming, and initiating infection in the host. Our phylogeny analysis of 1947 sequences of S proteins indicated there is a change in amino acid (aa) from aspartate (Group-A) to glycine (Group-B) at position 614, near the receptor- binding domain (RBD; aa positions 331-524). The two variants are reported to be in circulation, disproportionately across the world, with Group-A dominant in Asia and Group-B in North America. The trimeric, monomeric, and RBD of S protein of both the variant groups (A & B) were modeled using the Swiss-Model server and were docked with the human receptor angiotensin-converting enzyme 2 (hACE2) employing the PatchDock server and visualized in PyMol. Group-A S proteinís RBD bound imperceptibly to the two binding clefts of the hACE2 protein, on the other hand, Group-B S proteinís RBD perfectly interacted inside the binding clefts of hACE2, with higher number of hydrogen and hydrophobic interactions. This implies that the S proteinís amino acid at position 614 near the core RBD influences its interaction with the cognate hACE2 receptor, which may induce its infectivity that should be explored further with molecular and biochemical studies.



SARS-CoV-2; Spike protein; hACE2; RBD; binding affinity; molecular docking; molecular modeling.



Baig et al. Bioinformation 17(2): 337-347 (2021)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.