In the span of 7 months, the COVID-19 pandemic has caused a devastating global health crisis with significant mortality and socioeconomic implications. As of July 23, 2020, more than 15 million cases and 622,000 attributable deaths have been reported worldwide (5–8) (https://coronavirus.jhu.edu/map.html). Phylogenetic analyses suggest that SARS-CoV-2 is likely derived from a clade of viruses found in horseshoe bats (9). In S, the bat genome RaTG13 has more than 97% amino acid identity with SARS-CoV-2 (6). Interestingly, the RmYN02 sequence, which is the closest to SARS-CoV-2 in the long ORF1ab but more distant than RaTG13 in S, showed the insertion of multiple amino acids at the cleavage site between the S1 and S2 subunits of the S protein (this S1/S2 insertion is a characteristic feature of SARS-CoV-2) (10). Highly similar sequences, especially in the RBD, were also identified in Malayan pangolins (11, 12), emphasizing the plasticity of coronavirus genomes and their propensity to switch hosts. Although the closest currently available bat sequences are fairly divergent from SARS-CoV-2, their characteristics (insertion at S1/S2 cleavage site, high diversity, and similarity between specific gene fragments and particular strains) together with their known adaptive properties (high recombination and host-switching rates and evidence of positive selection) support that these bat viruses constitute a generalist lineage where a specific virus is likely the natural origin of SARS-CoV-2. We did not study the transmission of the virus from its animal reservoir and focused our analysis on the evolution of SARS-CoV-2 since its introduction in humans. While the scale of the pandemic attests to the high transmissibility of SARS-CoV-2 between humans, with a basic reproduction number R0 estimated to be 2.2 (95% CI, 1.4 to 3.9) in Wuhan, China (13), we wanted to investigate evidence of further adaptation of SARS-CoV-2 to its host, as adaptive processes could interfere with vaccine efficacy.