The newly emerged variants make our fight against global pandemic tougher as these variants might provide an evolutionary advantage, are more transmissible and harder for immune systems to detect. The 20I / 501Y.V1 variant of the lineage B.1.1.7, first discovered in the UK, has eight major mutations in the spike genes that may affect vaccine efficiency, antibody therapy, and pose a threat of re-infection. In addition to remaining susceptible to antibody neutralization, the B.1.1.7 (alpha) variant does not seem to be a major burden for available vaccines15,16.
B.1.351 (Beta variant), a variant first encountered in South Africa, is of greater concern as this variant is incompliant to NTD mAbs neutralization, mainly due to E484K mutations. In addition, we have also evidence that B.1.351 was more opposing to neutralization by convulsive plasma (9.4-fold) and vaccinated sera (10.3–12.4-fold)17. The SARS-CoV-2 P.1, the Brazilian variant of B.1.1.28 lineage, has 10 mutations in spike gene viz. D614G, T20N, D138Y, L18F, R190S, and P26S in the NTD and K417T, E484K and N501Y in the RBD region and H655Y within the furin cleavage site. It shares mutations similar to B.1.35. P.1 on the same 3 RBD residues which are resistant to neutralization by the RBD targeted mAbs. Shared E484K mutation is the main culprit, which emerged in more than 50 lines independently along with B.1.526, recently identified in New York. A significant loss of neutralizing activity has been shown by vaccinated serum and convalescent plasma towards P.1, but the decrease is not as good as compared to what was found against B.1.351, Accordingly, the risk of re-infection by P.1 or dropped efficacy of vaccine protection may not be severe like B.1.35118.
The mRNA-1273 vaccine’s neutralizing activity towards number of variants like B.1.351, B.1.1.7 + E484K, B.1.1.7, P.1, B.1.427 / B.1.429, D614G, 20A.EU2, 20E [EU1], N439K-D614G, and previously identified mutant in Denmark mink cluster 5 were identified and found to have the same neutrality level as Wuhan-Hu-1 (D1414)19. Limited loss in antibody neutralizing activity against B.1.1.7 while significant loss against B.1.35 was shown by the AstraZeneca ChAdOx1 vaccine, thus maintaining its efficacy towards B.1.1.7 and demonstrating a major loss of efficacy against the benign version of B.1.151. Although the efficacy against B.1.1.7 was found to have retained by the BNT162b2 Pfizer / BioNTech COVID-19 vaccine. The Novavax vaccine (NVX-CoV2373) reported differential protective immunity in the clinical trials i.e. 96%, 60%, and 86% against parental strain, B.1.351 and B.1.1.7, respectively20. Many SARS-CoV-2 variants have been detected in the last few weeks of March in India. India is experiencing a sharp rise in coronavirus infections from between March and April 2021. Based on world meter statistics data https://www.worldometers.info/, we observed sudden enhancement of total, active, daily new cases, and death rate in the months of March and April indicates the beginning of second wave in India (Fig. 9). We also observed a sudden rise in the confirmed and active cases in all State/Union territory (UT) of India with sudden rise from March to April 2021 according to covid-19 India tracker (http://www.covid19india.org ) (Fig. 10 and Fig. 11). Based on these studies, it can be hypothesized that the B.1.617 may also one of the causes of the sudden increment of cases in all state and UT of India. It might be possible that B.1.617 plays a major role in speedy spreading of infections in India.
The consequences of the current examination propose that the new B.1.617 (along with 6 others RBD mutant strain) inside the receptor-restricting site could lessen the immunization adequacy and higher the probability of reinfections by influencing the SARS-CoV-2 connection with the CR3022 antibody and ACE2 receptor. Our docking analysis observed that the binding affinity of mutant strain with ACE2 receptor is increased and is low with antibody compared to other variants.
The RMSD, RMSF, Rg, SASA, Intramolecular H-bond and H-bond between protein and water molecules were plotted to analyze the stability as well as flexibility of structurally hampered mutant RBD variants. Comparison of wild with mutant RBD protein, significant RMSD fluctuations were observed in all variants (B.1.617 0.25–0.5 nm, E484K nm 0.25–0.4 nm, F486L 0.2–0.3 nm, K417G 0.2–0.4 nm, L455Y 0.2–0.4 nm, L455Y 0.2–0.4 nm, Q493N 0.2–0.4 nm and R408I 0.25–0.45 nm). However more fluctuation was observed in B.1.617 as compared to others. The RMSD output showed that the protein stability could be influenced. We observed lower RMSF values of variant in comparisons to wild that confirms the compressed behavior of mutant trajectory. Higher value of Rg was noticed in all mutants’ cases which indicate the possibility of lower compactness of protein. High fluctuations of SASA revealed that the protein structure and consequently protein function might be hampered. Fluctuations of total intra-molecular H-bond and H-bond between protein and water have been found in all structurally hampered RBD mutant variants which signify the rigidity of protein might be influenced21.
Previous study has disclosed that the residues F486, L455, Q493, and N501 in the RBD spike protein form a major binding domain for the human ACE2 receptor22. A few mutants’ viz.L455Y, Q493N, R408I, Q498Y, F486L, N501T within the RBD region (319–591), and D936Y& A930V within HR1 site (912–984) have also been studied by in silico analysis to investigate the basic structure of spike glycoprotein. After comparing MD simulations in mutants and WT, a significant destabilizing outcome of mutations on the HR1 and RBD domains was revealed. Researchers revealed compromised stability of the overall spike protein structures by investigating the effect of framed mutations, before binding to the receptor23.