Molecular adaptations during viral epidemics

In 1977, the world witnessed both the eradication of smallpox and the beginning of the modern age of genomics. Over the following half‐century, 7 epidemic viruses of international concern galvanized virologists across the globe and led to increasingly extensive virus genome sequencing. These sequencing efforts exerted over periods of rapid adaptation of viruses to new hosts, in particular, humans provide insight into the molecular mechanisms underpinning virus evolution. Investment in virus genome sequencing was dramatically increased by the unprecedented support for phylogenomic analyses during the COVID‐19 pandemic. In this review, we attempt to piece together comprehensive molecular histories of the adaptation of variola virus, HIV‐1 M, SARS, H1N1‐SIV, MERS, Ebola, Zika, and SARS‐CoV‐2 to the human host. Disruption of genes involved in virus–host interaction in animal hosts, recombination including genome segment reassortment, and adaptive mutations leading to amino acid replacements in virus proteins involved in host receptor binding and membrane fusion are identified as the key factors in the evolution of epidemic viruses. Graphical Abstract This review comprehensively describes the molecular adaptation of variola virus, HIV‐1 M, SARS, H1N1‐SIV, MERS, Ebola, Zika, and SARS‐CoV‐2 to the human host and identifies the key factors in the evolution of epidemic viruses.