In silico study suggests SARS-CoV-2 Omicron XBB.1.5 strain to be more infective than previous strains

By Pooja Toshniwal PahariaJan 23 2023Reviewed by Aimee Molineux

In a recent study posted to the bioRxiv* preprint server, researchers performed an in silico analysis to estimate the relative risks of recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented morbidity and mortality worldwide. The continual emergence of novel SARS-CoV-2 variants, with greater infectivity, virulence, transmissibility, and immune evasiveness, has challenged the efficacy of COVID-19 vaccines and other therapeutic agents such as monoclonal antibodies.

During the initial days of 2023, the BQ.1 subvariant, XBB.1 subvariant, and the XBB.1.5 subvariant of the Omicron variant were identified and estimated to enhance the risk of epidemics in times to come. Continuous SARS-CoV-2 surveillance efforts and genomic research are essential to improve understanding of the virological characteristics of novel SARS-CoV-2 variants and guide the development of updated, broad, and more effective anti-SARS-CoV-2 therapeutics.

The authors of the present study previously investigated the degree of infectivity for SARS-CoV-2 variants, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.1.529) subvariants, BA.1, Omicron BA.2 subvariant and the Omicron BA.2.75 subvariant in terms of a ratio per SARS-CoV-2 Wuhan-Hu-1 strain and the evolutionary distances of the variant spike (S) genes from that of the ancestral Wuhan-Hu-1 S.

About the study

In the present study, researchers extended their previous analysis by estimating epidemic risks for the recently emerged BQ.1 subvariant, XBB.1 subvariant, and XBB.1.5 subvariant of Omicron.

Molecular docking simulations of the S protein receptor binding domain (RBD) of BQ.1, XBB.1, and XBB.1.5 interactions with the ACE2 (angiotensin-converting enzyme 2) receptors of the host were performed to evaluate the binding affinities of SARS-CoV-2 variants and subvariants, with ACE2.

The spike gene sequences of the variants were retrieved from the NCBI database, and information on variant S protein mutations was obtained from the https://covariants.org website.

In addition, the evolutionary distances of spike genes of SARS-CoV-2 Alpha variant, Beta variant, Gamma variant, Delta variant, Omicron BA.1 subvariant, Omicron BA.2 subvariant, Omicron BA.4/5 subvariant, Omicron BA.2.75 subvariant, Omicron BQ.1 subvariant, Omicron XBB.1 subvariant and the Omicron XBB.1.5 Subvariant) from the S genes of Wuhan-Hu-1 strain, Omicron BA.1 and Omicron BA.4/5 variants, in absolute terms, were determined to assess SARS-CoV-2 evolutionary changes.

Results

The Omicron XBB.1.5 subvariant showed the greatest ACE2 binding affinity, indicating the greatest infectivity, weak effects of COVID-19 vaccines, and the greatest tendency to cause an epidemic in the future. The evolutionary distances of the Omicron BQ.1 subvariant, Omicron XBB.1 subvariant, and Omicron XBB.1.5 subvariant showed that the BQ.1 subvariant had a short phylogenetic distance from the Omicron BA.4/5 subvariant, indicating that Omicron BA.4/5 subvariant-based vaccines would be equivalently effective against the BQ.1 subvariant.

Further, the long distances of the XBB.1 subvariant and the XBB.1.5 subvariant from the Wuhan-Hu-1 S gene indicated that existing COVID-19 vaccines would be less effective against the subvariants, underscoring the need for updated vaccines.

The ACE2 binding affinities for spike proteins (in terms of ratios per SARS-CoV-2 Wuhan-Hu-1 strain) for the Wuhan-Hu-1 strain, Alpha variant, Beta variant, Gamma variant, Delta variant, Omicron’s BA.1 subvariant, Omicron BA.2 subvariant, Omicron BA.4/5 subvariant, Omicron BA.2.75 subvariant, Omicron BQ.1 subvariant, Omicron BQ.1 subvariant, Omicron XBB.1 subvariant, and XBB.1.5 subvariant were 1.0, 1.2, 1.2,1.3, 2.1, 1.6, 2.5, 2.2, 2.9, 3.1, 1.9, and 3.0, respectively.

The evolutionary distances for spike genes (from Wuhan-Hu-1 strain spike gene) x 10^-3 for Alpha, Beta, Gamma, Delta, BA.1, Omicron BA.2, Omicron BA.4/5, Omicron BA.2.75, Omicron BQ.1, Omicron BQ.1, Omicron XBB.1 and XBB.1.5, in absolute terms, were 2.1, 2.1, 3.5, 3.2, 11.5, 8.3, 9.2, 10.9, 10.0, 12.4, and 13.1, respectively.

The evolutionary distances of spike genes from BA.1 x 10^-3 for Omicron BA.2 subvariant, BA.4/5 subvariant, BA.2.75 subvariant, BQ.1 subvariant, XBB.1 subvariant and XBB.1.5 subvariant, in absolute terms, were 5.6, 6.5, 8.3, 7.4, 9.8, and 10.4, respectively. The evolutionary distances of the spike genes of the BQ.1 subvariant, XBB.1 subvariant and XBB.1.5 subvariant of Omicron from the Omicron BA.4/5 subvariant x 10^-3, in absolute terms, were 2.9, 0.9, 4.4, and 5.1, respectively.

Overall, the study findings showed that the XBB.1.5 subvariant of Omicron had the greatest affinity of binding with human ACE2 and the greatest phylogenetic distance from spike genes of Wuhan-Hu-1, Omicron BA.1, and Omicron BA.4/5. The findings indicated that XBB.1.5 might be more infective than previously circulating variants, underscoring the need for the greatest caution for XBB.1.5 infections.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.