Researchers are identifying a new SARS-CoV-2 variant (A.VOI.V2) in South Africa

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

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

background

Since its appearance in December 2019, SARS-CoV-2, the causative agent of 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 glycoprotein on the viral envelope needed to establish SARS-CoV-2 infection. Due to its robust immunogenicity, spike protein is considered to be the strongest target for the development of therapeutic antibodies and vaccines. An increased frequency of peak mutations in newly developed variants has raised the question of whether these mutations could affect the functionality of monoclonal antibodies and vaccines designed specifically against previously circulating viral variants.

Some recently emerging SARS-CoV-2 (VOC) concerns, such as the UK, South Africa and Brazil, have shown significantly higher transmissibility than previously circulating variants. Moreover, an increasing number of preliminary studies have suggested that these variants may be associated with increased virulence. Mutations found in these variants have been shown to increase the binding affinity between the peak receptor binding domain (RBD) and the angiotensin 2 conversion host receptor (ACE2). Furthermore, there is evidence that some of the peak RBD mutations facilitate the virus to escape antibody-mediated neutralization. These observations explain the reason behind the increase in VOC infectivity and virulence.

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

Study design

Shortly after its appearance at the end of 2020, the South African version of SARS-CoV-2 (line B.1.351) spread rapidly in over 50 countries globally and became the predominantly circulating strain in southern Africa. The current study was initiated to quickly characterize the transmission dynamics of this variant and other VOCs in Africa. The first report on SARS-CoV-2 genomic surveillance data in Angola was presented here.

Important remarks

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 come from lines B.1.351, B.1.1.7 and B.1.525; 44 come from line C.16 in Portugal; and 12 from other lines. In addition, they identified a new variant on three air passengers from Tanzania. Interestingly, three viral genomes isolated from these passengers showed an almost identical sequence. They have temporarily designated the new variant A.VOI.V2.

With further analysis, they noticed 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 spike protein. Specifically analyzing the spike mutations, they identified 3 substitutions in the RBD spike, 2 substitutions near the S1 / S2 cleavage site and 5 substitutions and 3 deletions in the N-terminal spike domain (NTD). Moreover, they observed that some of the NTD mutations are present in the antigenic supersite.

A) The phylogenetic tree of a subset of A-line sequences (n = 319) including five sequences from cases with a history of travel to Tanzania, three of which are A.VOI.V2 sampled in Angola (vertices presented with a triangle); B) Regression of genetic distances from root to peak to the sampling data, for sequences belonging to line A, presenting the novel A.VOI.V2 (red), the known VOI A.23.1 (light blue), other sequences of line A (blue intense), two of which are documented as having a history of travel in Tanzania (red outline); C) Violin diagram showing the number of amino acid mutations in the entire genome and the peak glycoprotein in a subgroup of genomes from 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 peak, NTD = Nterminal domain, RBD = receptor binding domain, RBM = receptor binding motif, S1 / S2 = S1 / S2 site cleavage, and the rest of the genome in gray).

A) The phylogenetic tree of a subset of A-line sequences (n = 319) including five sequences from cases with a history of travel to Tanzania, three of which are A.VOI.V2 sampled in Angola (vertices presented with a triangle); B) Regression of genetic distances from root to peak to the sampling data, for sequences belonging to line A, presenting the novel A.VOI.V2 (red), the known VOI A.23.1 (light blue), other sequences of line A (blue intense), two of which are documented as having a history of travel in Tanzania (red outline); C) Violin diagram showing the number of amino acid mutations in the entire genome and the peak glycoprotein in a subgroup of genomes from 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 peak, NTD = Nterminal domain, RBD = receptor binding domain, RBM = receptor binding motif, S1 / S2 = S1 / S2 site cleavage, and the rest of the genome in gray).

Study the meaning

The study identifies a new SARS-CoV-2 variant with multiple mutations. Most of these mutations are 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 the viral condition.

Although the new variant is identified in only three passengers in Tanzania, scientists believe that more investigations are needed to control its transmission to and from the source country.

*Important Note

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

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