Researchers identify a new SARS-CoV-2 variant (A.VOI.V2) in southern Africa

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A team of international scientists has recently explored the dynamics of transmission of currently circulating variants of severe acute respiratory syndrome (SARS-CoV-2) coronavirus 2 in a southern African country. By analyzing the genomic sequences of these variants, they have identified a new variant of SARS-CoV-2 with multiple ear mutations. They have temporarily designated the variant A.VOI.V2. A detailed description of the genomic surveillance they carried out in is currently available medRxiv* prepress server.

Study: Based on travel surveillance in Africa, a new variant of interest of SARS-CoV-2 with multiple peak mutations is identified. Image credit: joshimerbin / Shutterstock

Background

Since its appearance in December 2019, SARS-CoV-2, the pathogen causing coronavirus disease 2019 (COVID-19), has undergone more than 12,000 mutations. Most of these mutations are found in the spike viral protein, which is a viral envelope glycoprotein needed to establish a SARS-CoV-2 infection. Due to the robust immunogenicity, ear protein is considered to be the most potent target for the development of therapeutic antibodies and vaccines. An increase in the frequency of peak mutations in emerging variants has raised the question of whether these mutations could potentially affect the functionality of monoclonal antibodies and vaccines specifically designed against previously circulating viral variants.

Some recently emerged SARS-CoV-2 concern (VOC) variants, such as the UK, South Africa, and Brazil variants, have shown significantly higher transmissibility than previously circulating variants. In addition, a growing group of preliminary studies has suggested that these variants could be associated with increased virulence. Mutations found in these variants have been found to increase the binding affinity between the spike receptor binding domain (RBD) and the angiotensin converting enzyme 2 receptor (ACE2). In addition, there is evidence that some of the leading RBD mutations facilitate the virus to escape antibody-mediated neutralization. These observations explain the reason for the increase in infectivity and virulence of VOCs.

In the current study, scientists have conducted extensive genomic surveillance of SARS-CoV-2 variants throughout Angola, a country located on the west coast of southern Africa. The study was conducted by the South African Genomic Surveillance Network (NGS-SA) in partnership with the African Centers for Disease Control and Prevention and the African Society of Laboratory Medicine.

Study design

Shortly after its appearance in late 2020, the South African variant of SARS-CoV-2 (lineage B.1.351) has rapidly spread to more than 50 countries around the world and has become the strain predominantly circulating in southern Africa. The current study has been initiated to quickly characterize the transmission dynamics of this variant and other VOCs in Africa. The first report on genomic surveillance data from Angola’s SARS-CoV-2 has been presented here.

Important observations

The scientists analyzed a total of 118 nasopharyngeal samples collected between June 2020 and February 2021. Using these samples, they generated 73 high-quality SARS-CoV-2 genomes; of which, 14 were of lineages B.1.351, B.1.1.7 and B.1.525; 44 were of the C.16 lineage of Portugal; and 12 other lineages. In addition, they identified a new variant in three air passengers from Tanzania. Interestingly, three viral genomes isolated from these passengers exhibited an almost identical sequence. They temporarily designated the new variant A.VOI.V2.

With further analysis, they observed that the new variant has a total of 31 amino acid substitution mutations and 3 deletion mutations. Of these mutations, 11 of 31 substitution mutations and all deletion mutations were found in the ear protein. By specifically analyzing spike mutations, they identified 3 substitutions in the RBD spike, 2 substitutions close to the S1 / S2 cleavage site, and 5 substitutions and 3 deletions in the N-terminal spike domain (NTD). In addition, they observed that some of the NTD mutations are present in the antigenic supersite.

A) Phylogenetic tree of a subset of lineage sequences A (n = 319) that includes five case sequences with travel history of Tanzania, three of which are A.VOI.V2 sampled in Angola (tips shown with a triangle ); B) Regression of the genetic root-to-tip distances against the sampling dates, for sequences belonging to lineage A, showing the novel A.VOI.V2 (red), the well-known VOI A.23.1 (light blue), other sequences of lineage A (deep blue), two of which are documented with travel history from Tanzania (red outline); C) Violin diagram showing the number of amino acid mutations throughout the genome and spike glycoprotein in a subset of genomes of five known variants compared to the novel A.VOI.V2; D) Genome map showing the position of the 31 amino acid substitutions and three deletions (color tip, NTD = Nterminal domain, RBD = receptor binding domain, RBM = receptor binding motif, S1 / S2 = S1 / S2 cleavage site, and the rest of the genome in gray).

A) Phylogenetic tree of a subset of lineage sequences A (n = 319) that includes five case sequences with travel history of Tanzania, three of which are A.VOI.V2 sampled in Angola (tips shown with a triangle ); B) Regression of the root-to-tip genetic distances against the sampling dates, for sequences belonging to the A lineage, showing the novel A.VOI.V2 (red), the well-known VOI A.23.1 (light blue), other sequences of lineage A (deep blue), two of which are documented with travel history from Tanzania (red outline); C) Violin diagram showing the number of amino acid mutations throughout the genome and spike glycoprotein in a subset of genomes of five known variants compared to the novel A.VOI.V2; D) Genome map showing the position of the 31 amino acid substitutions and three deletions (color tip, NTD = Nterminal domain, RBD = receptor binding domain, RBM = receptor binding motif, S1 / S2 = S1 / S2 cleavage site, and the rest of the genome in gray).

Importance of the study

The study identifies a new variant of SARS-CoV-2 with multiple tip mutations. Most of these mutations are also present in other VOCs and are known to increase viral infectivity and antibody resistance. These observations indicate that, in response to certain selective pressures, these mutations gradually evolve under positive selection and improve viral form.

Although the new variant is only identified in three Tanzanian passengers, scientists believe more research is needed to control its transmission in and out of the country of origin.

* Important news

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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