Unbuttoning the impact of N501Y mutant RBD on viral entry mechanism: A computational insight

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a serious global threat. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for this pandemic has imposed a severe burden on the medical settings. The spike (S) protein of SARS-CoV-2 is an important structural protein playing a key role in the viral entry. This protein is responsible for the receptor recognition and cell membrane fusion process. The recent reports of the appearance and spread of new SARS-CoV-2 strain has raised alarms. It was reported that this new variant containing the prominent active site mutation in the RBD (N501Y) was rapidly spreading within the population. The reported N501Y mutation within the spike’s essential part, known as the ‘receptor-binding domain’ has raised several questions. Here in this study we have tried to explore the effect of N501Y mutation within the spike protein using several in silico approaches

The Emergence and Spread of Novel SARS-CoV-2 Variants

“…Three mutations in S gene of these mutations have potential biological effects: First, mutation N501Y is located in the receptor-binding motif (RBM), one of the six key contact residues within the receptor-binding domain (RBD), and has been identified to enhance the affinity of the virus to ACE2 ( 20 , 21 ). Second, 69–70 deletion may lead to conformational changes of S protein that it is structural changes, which is conducive to the escape of the virus from the immune response of the host ( 22 ).…”

Molecular Level Dissection of Critical Spike Mutations in SARS‐CoV‐2 Variants of Concern (VOCs): A Simplified Review

“…The aromatic ring of Y501 gets sandwiched between Y41 and K353 of the hACE2 receptor and consequently the benzene ring edge forms the perpendicular π-π stacking interaction with the benzene ring surface of Y41, and simultaneously Y501 benzene ring surface also interacts hydrophobically with the alkane chain in K353 as shown in Figure 4(b). [62][63][64] Overall, the N501Y mutation induces few additional associations with hACE2: (i) potentially π-stacking interaction with Y41 residue and (ii) a cation-π interaction with K353 residue (iii) a hydrogen bond with D38 residue (iv) Increased salt-bridge electrostatic interaction between T500 and D355 in the RBD and hACE2 respectively. [65,66] These new associations results in an increase in hACE2-binding affinity which furthers effects the infectivity.…”