Inactivated SARS-CoV-2 Variant B.1.1.7 (England/204820464/2020)

The first designated SARS-CoV-2 variant of concern (VOC) was the B.1.1.7 lineage, later named Alpha by the World Health Organization. This variant originated in early autumn but was discovered in December 2020 and spread rapidly, causing widespread infection worldwide. The Alpha variant is notable for its long ancestral phylogenetic branching and high evolutionary rate. The Alpha genome comprises a well-supported monophyletic clade, with an evolutionary rate typical of SARS-CoV-2. Compared to contemporaneous lineages, the Alpha variant contains 14 lineage-specific amino acid substitutions and 3 deletions, which were unprecedented in global SARS-CoV-2 viral genomic datasets at the time of its emergence. The variant''s mutational profile includes some that have arisen independently in other VOCs. Experimental data indicate that it enhances binding affinity to human and mouse angiotensin-converting enzyme 2 (ACE2) and is associated with increased infectivity and virulence in mouse models.

Two other notable deletions exist in the spike gene of Alpha: a six-base-pair deletion at position 21765 (amino acid positions 69-70) and a three-base-pair deletion at position 21991 (amino acid position 144). Both deletions have been previously reported in chronically infected individuals. The former has also been linked to a rapid outbreak in Danish mink and has been shown to enhance infectivity in vitro. The latter has been shown to block binding of monoclonal antibodies and, to a lesser extent, convalescent antisera, and exhibit reduced neutralization efficacy. Furthermore, a nine-base-pair deletion exists in Alpha''s nonstructural protein 6 (NSP6), also present in VOCs Beta, Gamma, and Omicron. This deletion is located on the exterior of the autophagic vesicle and theoretically limits its expansion. A mutation also exists in the accessory protein open reading frame 8 (ORF8), shortening the protein from 121 amino acids to only 27, potentially leading to loss of function and allowing further downstream mutations to occur.