February 2021: We report here newly emerging A sub-lineages, A.23 and A.23.1, encoding replacements in the spike protein, nsp6, ORF8 and ORF9, with A.23.1 the major virus lineage now observed in Kampala.
Of concern, the recent Kampala and global A.23.1 virus sequences from December 2020-January 2021 now encoded 4 or 5 amino acid changes in the spike protein (now defining lineage A.23.1, see below) plus additional protein changes in nsp3, nsp6, ORF8 and ORF9 (Figure 3, 4). The P681R spike change encoded by all recent Kampala genomes since December 2020 adds a basic amino acid adjacent to the spike furin cleavage site. This same change has been shown in vitro to enhance the fusion activity of the SARS-CoV-2 spike protein, likely due to increased cleavage by the cellular furin protease (23); importantly, a similar change (P681H) is encoded by the recently emerging VOC B.1.1.7 that is now spreading globally across 75 countries as of 5 February 2021 (5) (24). There are also changes in the spike N-terminal domain (NTD), a known target of immune selection, observed in samples from Kampala A.23.1 lineage, including P26S and R102I plus 8 additional singleton changes (observed in only one genome,