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Influenza and coronaviruses, zoonotic respiratory RNA viruses, cause global pandemics with major public health issues. These viruses exist as quasispecies due to the to rapid evolution driven by their error-prone viral RNA polymerases and/or genomic organizations. They also show similar waves of infections/cases during the pandemic. However, there are some dissimilarities like severe disease in coronaviruses is due to cytokine-induced hyperactivity of the immune system, while secondary bacterial infection is a significant cause of death in influenza. Furthermore, unlike coronavirus, the segmented nature of influenza virus genome makes it easier for new strains to emerge through genetic reassortment, making its prevention and control more difficult. In this mini-review, we summarize the historical events of influenza and coronavirus pandemics or epidemics and the roles played by RNA viral genomes and pathogenesis in modulating viral evolution and generation of pandemic strains. Collectively, influenza and coronavirus diagnostics, vaccination, and other measures are critical for mitigating and controlling future pandemics. These pandemics might be regarded as a wake-up call to prepare us for future disasters