The rapid outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. The pandemic has affected millions of individuals and has already claimed more than 4.75 million lives. SARS-CoV-2 also continues to evolve owing to mutations, which have given rise to various SARS-CoV-2 variants.
Study: A novel B.1.1.523 SARS-CoV-2 variant that combines many spike mutations linked to immune evasion with current variants of concern. Image Credit: Oleksandra Kletsova / Shutterstock.com
*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.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
Due to the continuous surveillance of the SARS-CoV-2 genome across the world, many variants have been detected that are more infectious and virulent than the original strain first reported in Wuhan, China in 2019. As the data on these variants are shared through the Global initiative on sharing all influenza data (GISAID) database, scientists are able to better understand the evolution of SARS-CoV-2.
The United States Centers for Disease Control and Prevention (CDC) and the European Centre for Disease Prevention and Control (ECDC) have classified emerging SARS-CoV-2 variants as variants of concern (VoC) or variants of interest (VoI). Variants categorized as VoCs can cause severe COVID-19, increased rate of transmission, and can escape immune protection elicited via vaccine or natural infection. Some examples of known VoCs include the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), and Delta (B.1.617.2) variants.
Previous studies have reported that VoCs contain several mutations at the spike protein that are linked to immune evasion. In addition to the SARS-CoV-2 spike protein, neutralizing antibodies also target the receptor-binding domain (RBD) and N-terminal domain (NTD) of the virus.
Researchers have identified antigenic supersites in three regions of the NTD and found that some antibodies can effectively target these antigenic super sites and neutralize them. Prior studies have indicated that mutation at the RBD region (e.g., E484K) can result in the evasion of immune responses.
Identification and prevalence of a new SARS-CoV-2 variant
A new study published on bioRxiv* preprint server describes a new variant that possesses a novel combination of various concerning mutations at the spike region. These mutations have been reported to be shared among VoCs. The researchers of this study also revealed that the prevalence of this new variant has already been reported in many countries across the world.
Scientists defined the pangolin lineage of this variant to be B.1.1.523 and it was originally recognized as a variant under monitoring on July 14, 2021. According to GISAID, a total of 533 cases of B.1.1.523 have been reported as of August 19, 2021.
A number of cases of this variant have been reported in Russia and Germany. The prevalence of this variant has also been reported in the U.S. and Australia.
According to sequence-based surveillance data, the first cases concerning this variant were reported in February 2021. The frequency of this variant increased in May 2021 and its prevalence decreased by June 2021. Scientists have observed that this variant does not infect any specific age group.
In the current study. The researchers explain that it has not been easy to identify the origin of this variant by knowing the pangolin lineage and some spike mutations. Using the genomic sequences, they constructed a phylogenetic tree which revealed that all the cases were similar, as they were in the same branch. This result indicated that the origin of this virus was likely in Russia and the first strain was reported in Moscow.
Why are scientists concerned about this variant?
Two of the main reasons why scientists are concerned about this variant are the three amino acid deletions in the NTD antigenic supersite and the presence of the E484K mutation of the spike protein. The E484K mutation is also present in B.1.351 and P.1 variants, both of which are strongly associated with the reduced efficacy of vaccines.
Researchers conducted multiple sequence alignment (MSA) with the amino acid sequence of VoC and the original SARS-CoV-2 strain. They found that three VoCs (Alpha, Beta, and Delta) have deletions in one of the regions of the NTD antigenic supersite. The deletion of B.1.1.523 was found to be similar to B.1.617.2 and also comprises the E484K mutation that is present in many VOC. The results of this study are in line with previous studies that reported the effect of spike mutations on the efficacy of monoclonal antibodies and convalescent plasma treatment.
Conclusion
The authors of this study have reported that the B.1.1.523 variant harbors a new combination of concerning spike mutations that are present in many currently circulating VoCs. Many of these mutations are concerning and are associated with the evasion of immune protection.
This is critical, as these developments could challenge the effectiveness of available vaccines. More research is required to determine the transmissibility of this variant, which would assist in the development of preventive strategies to stop the further spread of this strain.
*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.
SARS-CoV-2 hijacks host proteins to escape immune clearance