Omicron and Delta Variant of SARS-CoV-2: A Comparative Computational Study of Spike protein

Abstract

Emerging SARS-CoV-2 variants, especially those of concern, may have an impact on the virus’s transmissibility and pathogenicity, as well as diagnostic equipment performance and vaccine effectiveness. Even though the SARS-CoV-2 Delta variant (B.1.617.2) emerged during India’s second wave of infections, Delta variants have grown dominant internationally and are still evolving. On November 26, 2021, WHO identified the variant B.1.1.529 as a variant of concern, naming it Omicron, based on evidence that Omicron contains numerous mutations that may influence its behaviour. However, the mode of transmission and severity of the Omicron variant remains unknown. We used computational studies to examine the Delta and Omicron variants in this work and found that the Omicron variant had a higher affinity for human ACE2 than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor binding domain, indicating a higher potential for transmission. Based on docking studies, the Q493R, N501Y, S371L, S373P, S375F, Q498R, and T478K mutations contribute significantly to high binding affinity with human ACE2. In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. These amino acids are located within the protein’s core and are required for structural stability. Omicron has a higher percentage of alpha-helix structure than the Delta variant in both whole spike protein and RBD, indicating that it has a more stable structure. We observed a disorder-order transition in the Omicron variant between spike protein RBD regions 468-473, and it may be significant in the influence of disordered residues/regions on spike protein stability and binding to ACE2. A future study might investigate the epidemiological and biological consequences of the Omicron variant.

Simulation of the omicron variant of SARS-CoV-2 shows broad antibody escape, weakened ACE2 binding, and modest increase in furin binding

“…Against an immunity background tuned to the delta variant, omicron will be more transmissible. (Note that two other studies suggest stronger ACE2 binding from omicron [31,33].) Experimental studies of the binding of the RBD to ACE2 and the FCD to furin will be needed to confirm these predictions.…”

SARS‐CoV‐2 Omicron variant: Characteristics and prevention

“…9 It is speculated that the Omicron variant might have been gestated in immunocompromised individuals (e.g., HIV patients co-infected by SARS-CoV-2) for a certain period of time, or it might have evolved in a nonhuman species and is just recently spilled back into human beings. 10…”

The electrostatic potential of the Omicron variant spike is higher than in Delta and Delta‐plus variants: A hint to higher transmissibility?

“…8 If a direct relationship between the electrostatic potential and receptor affinity, then infectivity exists, then the omicron VOC is expected to be more transmissible as some initial data do indeed suggest. 9,10 In addition, a marked modification of the surface electrostatic potential in Omicron RBD could alter interactions with other macromolecules such as antibodies.…”