The possible formation of population gene pools of zoonotic viruses with a respiratory route of transmission and a possibility of a pandemic at different stages of biosphere evolution is analyzed. Forming of Poxviruses (Entomopoxvirinae) gene pool could be the beginning of transformation from Plants to Arthropoda (Carbon – 375 million years ago) with further evolution connected with Rodentia (Pliocene – 75–70 million years ago) and further separation of genera (500–300 thousand years ago), and respiratory transmission (epidemics) between humans (10–2 thousand years BC). Smallpox comeback would be possible. Orthomyxoviruses relicts (genus Isavirus) were possibly connected with Ichthya (Silurian – 500–410 million years ago), and then close interaction with Aves (the Cretaceous, 125–110 million years ago) with the division of genera and respiratory transmission (epidemics) between humans (10–2 thousand BC). Next pandemic of influenza A could be catastrophic in terms of the number of victims and economic damage. Coronaviruses formed a gene pool by interaction with Amphibia (subfamily Letovirinae) and then with Chiroptera in Tertiary (110–75 million years ago) with transformation to Artiodactyla (Eocene – 70–60 million years ago), and only 10–2 thousand years BC acquired the ability to a respiratory transmission and became Alphaviruses, a seasonal infection of humans. A similar situation is possible in the near future with SARS-CoV-2. Pandemics associated with zoonoses even more serious than COVID-19 are likely. Constant monitoring of populational gene pools of zoonotic viruses is necessary. © LVOV D.K., GULYUKIN M. I., ZABEREZHNIY A.D., GULYUKIN F.V., 2020