Genomic surveillance of SARS-COV-2 has revealed that in addition to many variants of interests, this virus has yielded four variants of concern, α, β, γ and δ, as designated by the World Health Organization. Delta variant has recently become the predominant pandemic driver around the world and yielded four different subvariants (δ1, δ2, δ3 and δ4). Among them, δ1 has emerged as the key subvariant that drives the pandemic in India, Europe and the USA. A relevant question is whether δ1 subvariant continues to evolve and acquires additional mutations. Related to this, this subvariant has acquired spike V1176F, a signature substitution of γ variant, and yielded a new sublineage, δ1F. The substitution alters heptad repeat 2 of spike protein and is expected to improve interaction with heptad repeat 1 and enhance virus entry. Moreover, there are δ1F sublineages encoding spike N501Y, A783, Q836E and V1264L. While N501Y is a signature substitution shared by α, β, γ variants, V1264L is a key substitution in a δ1 sublineage that is a major pandemic driver in Southeast Asia. The Q836E-encoding lineage carries an average of 50 mutations per genome, making it the most mutated variant identified so far. Similar to δ1 subvariant, δ2 subvariant has also acquired spike V1176F and yielded new sublineages. Together, these results suggest that V1176F is a recurrent spike substitution that is frequently acquired by SARS-COV-2 variants to improve viral fitness. It is thus important to track the evolutionary trajectory of related variants for considering and instituting the most effective public health measures.
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