AbstractThe origin of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the subject of many hypotheses. One of them, proposed by Segreto and Deigin, assumes artificial chimeric construction of SARS‐CoV‐2 from a backbone of RaTG13‐like CoV and receptor binding domain (RBD) of a pangolin MP789‐like CoV, followed by serial cell or animal passage. Here we show that this hypothesis relies on incorrect or weak assumptions, and does not agree with the results of comparative genomics analysis. The genetic divergence between SARS‐CoV‐2 and both its proposed ancestors is too high to have accumulated in a lab, given the timeframe of several years. Furthermore, comparative analysis of S‐protein gene sequences suggests that the RBD of SARS‐CoV‐2 probably represents an ancestral non‐recombinant variant. These and other arguments significantly weaken the hypothesis of a laboratory origin for SARS‐CoV‐2, while the hypothesis of a natural origin is consistent with all available genetic and experimental data.