Dynamics prediction of emerging notable spike protein mutations in SARS-CoV-2 implies a need for updated vaccines

Abstract

The spike protein of SARS-CoV-2 plays a crucial role in binding with the human cell surface, which causes its pathogenicity. This study aimed to predict molecular dynamics change of emerging variants in the spike protein. In this study, several structural biology tools, such as SuperPose, were utilized to study spike protein structures' thermodynamics, superimposition, and the spike protein disulphide bonds. This questions the current vaccines efficacies that were based on the Nextstrain clade 19A that first documented in Wuhan and lacks any variants. The prediction results of this study have exhibited the stabilizing role of the globally dominant variant, the D614G; clade 20A, and other variants in addition to their role in increasing the flexibility of the spike protein of the virus. The SuperPose findings have revealed a conformational change impact of D614G in allowing the polybasic Furin cleavage site ( 682 RRAR↓S 686 ) to be closer to the receptor-binding domain (RBD) and hence more exposed to cleavage. The presence of D614G in any clade or subclade, such as 20A, B.1.1.7 (20I/501Y.V1) or Alpha, B.1.351 (20H/501Y.V2) or Beta, P.1 (20J/501Y.V3) or Gamma, B.1.617.2 (21A/478K.V1) or Delta, has increased its stability and flexibility and unified the superimposition among all clades which might impact the virus ability to escape the antibodies neutralization by changing the antigenicity drift of the protein three-dimensional (3D) structure from the wild type clade 19A; this is in agreement with previous study. In conclusion, a new design for the current vaccines to include at least the mutation D614G is immediately needed.

Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir

“…[13] A possible reformulation of the vaccines adjusted to currently circulating lineages of SARS-CoV-2 is being investigated. [14] , [15] , [16] The deployment of vaccines clearly remains the best public health measure to control the spread of SARS-CoV-2 and the severe health effects of COVID-19. [17] , [18] …”

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

“…Although of significant value, even the currently available vaccines are not without occasional serious side effects [26][27][28]. Moreover, the efficacy of the vaccines has decreased as the virus has mutated [29,30]. Already, there are several variants that have been identified and there will likely be others that may further reduce the effectiveness of the vaccines.…”

Potential linear B-cells epitope change to a helix structure in the spike of Omicron 21L or BA.2 predicts increased SARS-CoV-2 antibodies evasion

“…The T478K was reported as a mutation in the functional Receptor Binding Domain (RBD) associated with the infectivity and pathogenicity of any variants, where is it found ( Jhun et al, 2021c ). The biological meaning of this is that the previously reported mutation D614G was the reason for giving the spike protein a tendency to increase transmissibility and alter BNT162b2 vaccine-elicited neutralization when compared with the wild type spike protein without D614G ( Al-Zyoud and Haddad, 2021a ; Plante et al, 2021 ; Isabel et al, 2020 ).…”

“…No available data about G446 and T547K however, it was reported that G496S and Q493R, and Q498R have formed new salt bridges with residue D38 of the Angiotensin Converting Enzyme (ACE2) ( Mannar et al, 2022 ). It is worth mentioning here that the Omicron mutation E484A has increased the spike protein flexibility in a higher value of ΔΔS ENCoM value, giving 0.762 kcal.mol −1 .K −1 when compared with E484Q with a value of ΔΔS ENCoM value giving 0.389 kcal.mol −1 .K −1 and E484K with a value of ΔΔS ENCoM value giving 0.490 kcal.mol −1 .K −1 ( Al-Zyoud and Haddad, 2021a ), the mutation in amino acid 484 was previously reported as a mutation confer antibody resistance ( Liu et al, 2021a ). Specifically, it was reported that the mutation Q493R has conferred a simultaneous resistance to the treatment by the monoclonal antibodies, namely Bamlanivimab and Etesivimab ( Focosi et al, 2021 ).…”