In a latest research posted to the bioRxiv* preprint server, researchers characterised the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BQ.1.1 sub-variant.
Research: Convergent evolution of the SARS-CoV-2 Omicron subvariants resulting in the emergence of BQ.1.1 variant. Picture Credit score: Naeblys/Shutterstock
Background
SARS-CoV-2 Omicron BA.1 quickly supplanted the Delta variant, and shortly after, Omicron BA.2 was the predominant variant. After that, quite a few BA.2 descendants emerged, together with BA.2.75 and BA.5. Though BA.2.75 and BA.5 diverged from BA.2, they’re phylogenetically unbiased, and up to date research report comparable evolutionary patterns within the spikes of BA.2.75 and BA.5 sub-variants.
Beforehand, the authors reported a rise within the pathogenicity of BA.2.75 and BA.5 sub-variants in a hamster mannequin relative to the BA.2 sub-variant, suggesting that the sub-variants developed to boost intrinsic pathogenicity. Regardless of the emergence of a number of new sub-variants after BA.5, they’ve did not outcompete BA.5.
As an alternative, the emergent sub-variants look like below convergent evolution, buying amino acid substitutions on the similar web site. The BQ.1.1 sub-variant, a descendant of BA.5, harbors 5 convergent substitutions (R346T, K444T, L452R, N460K, and F486V) and has been labeled as a variant below monitoring by the World Well being Group (WHO).
The research and findings
Within the current research, researchers explored the evolutionary traits underlying the convergent evolution of SARS-CoV-2 Omicron lineages. First, they constructed phylogenetic bushes for Omicron sub-variants to establish the place convergent substitutions occurred. The L452 residue had the very best substitution frequency within the BA.2 lineage. Furthermore, substitution occasions have been comparatively extra frequent in newer lineages than BA.1/2.
Subsequent, the authors modeled the connection between spike substitutions and viral epidemic dynamics to evaluate the impression of substitutions on viral health. They analyzed a dataset of greater than 300,000 Omicron sequences collected between March 1, 2022, and October 15, 2022, that included 254 spike haplotypes. The 5 convergent substitutions positively affected the efficient reproductive quantity (Re).
Furthermore, the spike haplotype comparable to the BQ.1.1 sub-variant had the very best Re. Additional investigations indicated that viral health elevated independently in a number of Omicron lineages throughout BA.5 diversification. The evaluation additionally prompt that BQ.1.1 elevated its health by serially buying K444T, N460K, and R346T substitutions.
The researchers examined the immune resistance of SARS-CoV-2 Omicron BQ.1.1 utilizing pseudoviruses and noticed that BA.5 and BQ.1.1 have been markedly immune to neutralization by Omicron BA.2 breakthrough an infection sera. Notably, BQ.1.1 confirmed 2.7-fold elevated resistance to breakthrough an infection sera relative to BA.5. Equally, BQ.1.1 was 5.6-fold extra immune to BA.5 an infection sera than BA.5.
Sera from hamsters contaminated with BA.2, BA.2.75, or BA.5 exhibited excessive antiviral exercise in opposition to the infecting variant however lacked cross-reactivity in opposition to different variants. Yeast floor show (YSD) assay confirmed that the dissociation fixed (KD) of BQ.1.1 spike’s receptor-binding area (RBD) to human angiotensin-converting enzyme 2 (hACE2) was considerably decrease than that of BA.5 spike RBD, implying a better affinity of BQ.1.1 spike to hACE2 than BA.5 spike.
The N460K and R346T substitutions in BQ.1.1 spike have been implicated within the considerably enhanced binding affinity. Additional, BQ.1.1 pseudovirus confirmed increased infectivity than BA.2 or BA.5 pseudovirus. The R346T and N460K substitutions of the BQ.1.1 spike have been chargeable for the elevated infectivity. Syrian hamsters have been contaminated with scientific isolates of Delta, BA.5, or BQ.1.1.
The pulmonary operate of hamsters was decided based mostly on the ratio of time to peak expiratory movement relative to whole expiratory time (Rpef) and enhanced pause (Penh). Delta an infection brought about vital adjustments in these parameters than BA.5 an infection, suggesting that Delta was extra pathogenic than BA.5.
The Rpef and Penh of BQ.1.1-infected hamsters have been considerably increased and decrease than these of BA.5-infected animals, respectively. This meant that the pathogenicity of BQ.1.1 was akin to and even decrease than that of BA.5. Viral RNA load within the lungs of BA.5-infected hamsters was much like that of hamsters contaminated with Delta or Omicron BQ.1.1.
Lastly, the authors examined the intrinsic pathogenicity of SARS-CoV-2 Omicron BQ.1.1 by analyzing the proper lung of contaminated hamsters and scoring 5 histopathological options/parameters – 1) bronchitis/bronchiolitis, 2) hemorrhage with congestive edema, 3) alveolar injury, 4) hyperplasia of kind II pneumocytes, and 5) the realm of hyperplasia.
Delta-infected hamsters had a considerably increased cumulative histopathological rating than BA.5-infected animals. In distinction, the mixture scores have been comparable between hamsters contaminated with BA.5 and BQ.1.1, though BQ.1.1-infected animals confirmed enhanced bronchitis/bronchiolitis and extra kind II pneumocytes.
conclusions
To summarize, the authors uncovered the convergent evolution of sub-Omicron variants, highlighting the frequent substitutions at 5 websites within the viral spike protein that improved viral health and Re. SARS-CoV-2 Omicron BQ.1.1, which harbors all 5 convergent substitutions, confirmed the very best Re. The BQ.1.1 sub-variant was additionally extremely immune to neutralization by BA.2 or BA.5 breakthrough an infection sera and confirmed excessive binding affinity to hACE2 and higher fusogenicity than BA.5.
*Essential discover
bioRxiv publishes preliminary scientific experiences that aren’t peer-reviewed and, due to this fact, shouldn’t be thought to be conclusive, information scientific observe/health-related habits, or handled as established data.
