SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants

Abstract

Objectives: In our previous research, we have reported mathematical model with molecular simulation analysis to predict the infectivity of seven SARS-CoV-2 variants. In this report, we aimed to predict the relative risk of the recent new variants of SARS-CoV-2 based on our previous research. Methods: We subjected Omicron BA.4/5 or BA.2.75 variant of SARS-CoV-2 to the analysis for the evolutionary distance of the spike protein gene (S gene) to appreciate the changes of the spike protein. We performed the molecular docking simulation analyses of the spike protein with human angiotensin-converting enzyme 2 (ACE2) to understand the docking affinity in these variants. We then compared the evolutionary distance and the docking affinity of these variants with that of the seven variants which were analyzed in our previous research. Results: The evolutionary distance of the S gene in BA.4/5 or BA.2.75 from the Wuhan variant were longer than the other variants. The highest docking affinity of the spike protein with ACE2 (ratio per Wuhan variant) was observed in BA.2.75. Conclusion: It is important to note that BA.2.75 has both the highest docking affinity and the longest evolutionary distance of the S gene. These results suggest that the infection of BA.2.75 can be spread further than preexisting variants.

SARS-CoV-2 Omicron XBB.1.5 May Be a Variant That Spreads More Widely and Faster Than Other Variants

“…We obtained the information for the amino acid substitutions (see Table 1) of the spike proteins mostly from the CoVariants website (https://covariants.org). We then used the amino acid sequences for the analyses of the three-dimensional structures of each variant spike protein according to our previous research [1].…”

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

“…It carries K147E, W152R, F157L, I210V, G257S, D339H (mutated from G339D), G446S (which causes escape from cilgavimab and imdevimab), N460K, R493Q (reversion). R493Q and N460K cause BA.2.75 to exhibit higher ACE2-binding affinity than BA.2 and BA.4/BA.5( Cao et al, 2022b ; Saito et al, 2022 ) and the longest evolutionary distance of the S gene ( Sugano et al, 2022 ). BA.2.75 is neutralized by vaccine-elicited and BA.1/2 breakthrough infection-induced sera at the same levels of BA.2, but at lower level from convalescent sera than BA.2 and BA.5.…”

Vaccine- and BTI-elicited pre-Omicron immunity more effectively neutralizes Omicron sublineages BA.1, BA.2, BA.4 and BA.5 than pre-Omicron infection alone

“…In contrast, BA.2-elicited immunity confers cross-protection against BA.5 (16, 64, 77) and BA.2-offspring (16, 64, 77), emphasizing the beneficial impact of reactivation of NAbs targeting common epitopes. Importantly however, mixed immunity resulting from Omicron BA.1-and BA-2-breakthrough infections after 2 or 3 first generation vaccine doses or from reinfection after a first infection with a pre-Omicron strain or from bivalent vaccines combining wild-type + Omicron BA.1, wildtype + Omicron BA.4/5, Delta + Omicron BA.1 or hybrid Omicron BA.1/Delta determinants, all elicit superior NAb as well as T-cell responses against all Omicron sublineages and against pre-Omicron VOCs and confer better protection against severe forms of COVID-19 compared to boosters based on the original Wuhan strain or pre-Omicron (Beta or Delta) (3, 5, 16, 20, 38, 42, 53, 66, 67, 73, 75, 76, 78, 79). Accordingly, second generation bivalent vaccines combining ancestral and Omicron sequences (generally BA.1 or BA.4/BA.5) have been approved by the EMA and FDA in September 2022 as boosters after first generation vaccines based on the original Wuhan strain.…”

“…BA.2 sublineages BA.2.12.1, BA.2.75, BA.2.75.2, as well as BA.4, BA.5 and their offspring BA.4.6 and BQ.1.1 are gaining ground. These strains carry additional mutations which further increase their infectivity and antibody escape compared to the parental BA.2 (2)(3)(4)(5)(6)(7).…”

“…The Omicron lineage typically features strongly enhanced transmissibility compared to Delta and pre-Omicron variants (3-6, 19, 20). Increased transmissibility is due to its stronger docking to the receptor ACE2, and to its endocytosis-mediated, TMPRSS-2 independent entry into target cells, which also favors immune evasion (5,11,16,(21)(22)(23)(24)(25)(26)(27)(28)(29), although BA.5 can use the TMPRSS2 route (20). Furthermore, compensatory mutations have appeared in a number of strains to balance the loss replicative cost imposed by immune escape mutations (e.g.R493Q for F486V in BA.4/5 (2,30,31)).…”