Global Prevalence of Adaptive and Prolonged Infections’ Mutations in the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

Abstract

Several vaccines with varying efficacies have been developed and are currently administered globally to minimize the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite having an RNA-dependent RNA polymerase with a proofreading activity, new variants of SARS-CoV-2 are on the rise periodically. Some of the mutations in these variants, especially mutations on the spike protein, aid the virus in transmission, infectivity and host immune evasion. Further, these mutations also reduce the effectiveness of some of the current vaccines and monoclonal antibodies (mAbs). In the present study, using the available 984,769 SARS-CoV-2 nucleotide sequences on the NCBI database from the end of 2019 till 28 July 2021, we have estimated the global prevalence of so-called ‘adaptive mutations’ and ‘mutations identified in the prolonged infections’, in the receptor-binding domain (RBD) of the spike (S) protein. Irrespective of the geographical region, in the case of the adaptive mutations, N501Y (48.38%) was found to be the dominant mutation followed by L452R (17.52%), T478K (14.31%), E484K (4.69%), S477N (3.29%), K417T (1.64%), N439K (0.7%) and S494P (0.7%). Other mutations were found to be less prevalent (less than 0.7%). Since the last two months, there has been a massive increase of L452R and T478K mutations (delta variant) in certain areas. In the case of prolonged infections’ mutations (long-term SARS-CoV-2 infections), V483A (0.009%) was found to be dominant followed by Q493R (0.009%), while other mutations were found in less than 0.007% of the studied sequences. The data obtained in this study will aid in the development of better infection control policies, thereby curbing the spread of this virus.

Spike protein of SARS-CoV-2 variants: a brief review and practical implications

“…- Structural: the Docking Energy of Omicron RBD-ACE2 for this mutation was − 581.53 and decreased protein stability − 0.17 [ 120 ]. A high negative impact on biding was also reported for this mutation [ 204 ] a . Lower biding free energy when compared with Q493 [ 205 ] G496S RBD - Immune: it might be related to immune evasion of NAbs in Group A-D, which target the ACE2-bindind motif [ 180 ] - Structural: enhanced the S1-RBD binding by 13 folds in Alpha and Beta models [ 204 ] a .…”

“…A high negative impact on biding was also reported for this mutation [ 204 ] a . Lower biding free energy when compared with Q493 [ 205 ] G496S RBD - Immune: it might be related to immune evasion of NAbs in Group A-D, which target the ACE2-bindind motif [ 180 ] - Structural: enhanced the S1-RBD binding by 13 folds in Alpha and Beta models [ 204 ] a . The Docking Energy of Omicron RBD-ACE2 for this mutation was − 505.58 and decreased protein stability − 1.22 [ 120 ] The mutations were searched in Scielo®, Google academic®, and CAPES Periodicals by the name of the mutation and the words “mutation” and “spike”.…”

“…The presence of neutralizing antibodies C121 and C141 enriched the appearance of Q493R mutation [ 211 ]. Also, together with E484A and Q493R may disrupt the antibody Regdanvimab by Celltrion [ 179 ] - Structural: enhanced the S1-RBD biding[ 210 ] by 98 folds in Alpha and Beta models [ 204 ] a . The Docking Energy of Omicron RBD-ACE2 for this mutation was − 527.38 and decreased protein stability − 0.17 [ 120 ].…”

“…The Docking Energy of Omicron RBD-ACE2 for this mutation was − 527.38 and decreased protein stability − 0.17 [ 120 ]. It promotes a significant change in free energy (− 1.92 kcal/mol), contributing to a higher binding to the receptor, using Alpha and Beta variants as a model [ 204 ]. Helped, along with N460K and E484K, to strengthen de electrostatic complementarity between RBD and ACE2 [ 206 , 212 , 213 ].…”

Establishment of a pseudovirus neutralization assay based on SARS-CoV-2 S protein incorporated into lentiviral particles

“…A codon-optimized cDNA encoding the S protein and 3×FLAG tag was synthesized, with C-terminal 19 amino acid deletion to decrease endoplasmic reticulum (ER) location for facilitating incorporation of S protein into pseudovirons [12] , [13] . We also generated S-D614G, S-N501Y, and S-Delta mutation plasmids based on pc-S (WT) plasmid, which exhibit the prevalent substitution mutations around 6000 SARS-CoV-2 S variants globally [14] , [15] , [16] . The construction of SARS-CoV-2 S-WT protein expression plasmid and detailed information of different S mutant protein sequences are shown in Fig.…”