Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

Abstract

Among the multiple SARS-CoV-2 variants recently reported, the delta variant has generated most perilous and widespread effects. Another variant, omicron, has been identified specifically for its high transmissibility. Omicron contains numerous spike (S) protein mutations and in numbers much larger than those of its predecessor variants. BA.2, a sub variant of omicron, has recently emerged with more spreadable infectivity as compared to the original omicron species. BA.2 also contains several new and additional mutations in its spike protein, and represents the globally most prevalent form of SARS-CoV-2 at the present time.In this report we discuss some essential structural aspects and time-based structure changes of a selected set of spike protein mutations within the delta and omicron variants, including those of omicron BA.2. The expected impact of multiple-point mutations within the spike protein’s receptor-binding domain (RBD) and S1 are also discussed. It is expected that the structural data discussed in this report will be helpful to identify drug targets and to neutralize antibodies for the evolving variants/sub variants of SARS-CoV-2.

Prevalence of symptoms, comorbidities, and reinfections in individuals infected with Wild-Type SARS-CoV-2, Delta, or Omicron variants: a comparative study in western Mexico

“…At a molecular level, key virus mutations located in the S protein receptor-binding domain (RBD) are critical for the antibody resistance and infectivity of the SARS-CoV2 variant ( 8 ). In this sense, the Delta variant generated the most hazardous and widespread effects ( 9 ). Specifically, some reported mutations that had a more significant biological impact in this VOC were L452R and T478K, both of which are also present in the Omicron VOC ( 10 ).…”

Rapid Spread of Omicron Sub-Lineage as Evidence by Wastewater Surveillance

“…The ability of a VOC to replace the existing dominant one is a function of how its mutations permit attachment to host cells effectively and allow it to evade the body's immune responses [28][29][30]. For instance, BA.2 shares 32 mutations with BA.1 but has 28 distinct mutations [29,31]; thus, it has the potential to reinfect patients originally infected with BA.1, thereby allowing BA.1 to displace it as the dominant VOC.…”

“…Similarly, BA.5 shares a common genetic origin with BA.2 except for the additional L452R and F486V mutations, which enabled it to replace BA.2 [25]. The type of mutations present in each VOC or its sublineages have played a crucial role in their stability and transmissibility [30]; hence, these might be some of the key factors affecting their ability to replace the existing VOC.…”

Molecular evolutionary analysis of the SARS-CoV-2 through the mutation analysis of Spike, Envelope and RdRp proteins

“…Later, in September 2023, a new variant, BA.2.86 (or Pirola), was recommended for monitoring and was described as more resistant to monoclonal antibodies (mAbs) having ~35 mutations distinct from XBB.1.5 (Qu et al, 2023). BA.2.86 was also described as stable mutational variant, with higher affinity for receptor interactions, giving it a potential for increased severity and transmissibility (Roy, 2023). It was noted that the combination of N501Y, E484K, and K417N/T mutations could significantly affect the resistance and sensitivity to the currently designed therapy to control the infection (Akkız, 2022).…”