  Although lessons have been learned from previous severe acute respiratory
syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, the
rapid evolution of the viruses means that future outbreaks of a much larger
scale are possible, as shown by the current coronavirus disease 2019 (COVID-19)
outbreak. Therefore, it is necessary to better understand the evolution of
coronaviruses as well as viruses in general. This study reports a comparative
analysis of the amino acid usage within several key viral families and genera
that are prone to triggering outbreaks, including coronavirus (SARS-CoV-2,
SARS-CoV, MERS-CoV, HCoV-HKU1, HCoV-OC43, HCoV-NL63, HCoV-229E), influenza A
(H1N1, H3N2), flavivirus (dengue virus serotypes 1-4, Zika) and ebolavirus
(Zaire, Sudan, Bundibugyo ebolavirus). Our analysis reveals that the
distribution of amino acid usage in the viral genome is constrained to follow a
linear order, and the distribution remains closely related to the viral species
within the family or genus. This constraint can be adapted to predict viral
mutations and future variants of concern. By studying previous SARS and MERS
outbreaks, we have adapted this naturally occurring pattern to determine that
although pangolin plays a role in the outbreak of COVID-19, it may not be the
sole agent as an intermediate animal. In addition to this study, our findings
contribute to the understanding of viral mutations for subsequent development
of vaccines and toward developing a model to determine the source of the
outbreak.
