Physicochemical effect of the N501Y, E484K/Q, K417N/T, L452R and T478K mutations on the SARS-CoV-2 spike protein RBD and its influence on agent fitness and on attributes developed by emerging variants of concern

Quasispecies Analysis of SARS-CoV-2 of 15 Different Lineages during the First Year of the Pandemic Prompts Scratching under the Surface of Consensus Genome Sequences

“…We have been attentive in the present study to the intra-sample diversity at spike nucleotide positions where mutations have been reported to occur that are hallmarks of SARS-CoV-2 variants of concern, and that are critical for immune escape and were reported to emerge during prolonged infection of immunocompromised patients, at codons 417, 452, 484, 501, 614, and 681 [ 38 ]. Amino acid substitution K417N is a hallmark of the Omicron variants, occurs in a neutralizing epitope, and has been suspected to be associated with escape from neutralization by some classes of monoclonal antibodies and convalescent patients’ serum samples, and to contribute to escape from neutralization by antibodies elicited by mRNA vaccines [ 55 ]. Amino acid substitution L452R is a hallmark of the Delta variant but also occurred independently in several other variants, indicating convergent evolution, suggesting that this amino acid substitution could result in viral adaptation due to increasing immunity at the population scale, and it has been shown to reduce neutralization by several monoclonal antibodies and convalescent patients’ plasma [ 56 ].…”

“…Amino acid substitution L452R is a hallmark of the Delta variant but also occurred independently in several other variants, indicating convergent evolution, suggesting that this amino acid substitution could result in viral adaptation due to increasing immunity at the population scale, and it has been shown to reduce neutralization by several monoclonal antibodies and convalescent patients' plasma [56]. Amino acid substitution E484K is located in the receptor binding domain of the spike protein, enhances binding affinity to ACE2, and is also located in a major virus neutralization site and decreases binding affinity of some neutralizing antibodies [55]. Another amino acid substitution at this position, E484Q, which could weaken virus binding to ACE2, is a hallmark of the Delta variant (https://covariants.org (accessed on 30 September 2022)) [40,55].…”

“…Amino acid substitution E484K is located in the receptor binding domain of the spike protein, enhances binding affinity to ACE2, and is also located in a major virus neutralization site and decreases binding affinity of some neutralizing antibodies [55]. Another amino acid substitution at this position, E484Q, which could weaken virus binding to ACE2, is a hallmark of the Delta variant (https://covariants.org (accessed on 30 September 2022)) [40,55]. Amino acid substitution N501Y is located within the receptor binding motif of the spike S1 subunit and enhances virus binding affinity to the host cell.…”

“…Amino acid substitution N501Y is located within the receptor binding motif of the spike S1 subunit and enhances virus binding affinity to the host cell. It has been a hallmark mutation of several variants including the Alpha, Beta, Gamma, and Omicron variants (https://covariants.org (accessed on 30 September 2022)) [40,55]. Amino acid substitution D614G favors an open conformational state for the spike and was associated with increased infectiousness in vitro, with increased viral loads in the upper airways, and was suspected to be associated with a higher rate of profitable binding with the host receptor [57,58].…”

Investigating the mutations in the SARS-CoV-2 proteins among European countries

“…According to Chen et al, S477N and T478K are dependent on each other [19]. Although the information on the physiological impact of T478K is conflicting, it is clear that the variant enhances infectivity [22]. Also, it could be effective in helping the virus evade antibody neutralization and impairing the interaction of RBD with drugs [23, 24].…”