Serine 477 plays a crucial role in the interaction of the SARS-CoV-2 spike protein with the human receptor ACE2

Amit Singh, Georg Steinkellner, Katharina Köchl, Karl Gruber, Christian C. Gruber

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Received date: 15th November 2020

Since the worldwide outbreak of the infectious disease COVID-19, several studies have been published to understand the structural mechanism of the novel coronavirus SARS-CoV-2. During the infection process, the SARS-CoV-2 spike (S) protein plays a crucial role in the receptor recognition and cell membrane fusion process by interacting with the human angiotensin-converting enzyme 2 (hACE2) receptor. However, new variants of these spike proteins emerge as the virus passes through the host reservoir. This poses a major challenge for the design of a potent antibody against these spike proteins. Through structural bioinformatics analysis based on normal mode analysis (NMA) we identified a highly flexible region in the receptor binding domain (RBD) of SARS-CoV-2, starting from residue 475 up to residue 485. Structurally, S477 shows the highest rotational degrees of freedom among them. At the same time, S477 is the world’s most frequently mutated residue in the RBD of SARS-CoV-2. Therefore, using advanced MD simulations, we have investigated the role of S477 and its two frequent mutations (S477G and S477N) at the RBD during the binding to hACE2. We found that the amino acid exchanges S477G and S477N strengthen the binding of the SARS-COV-2 spike with the hACE2 receptor.

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This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.

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Nature Research, Springer Nature