Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14). The newly isolated viruses harbour more proteins than the old ones. Therefore, identifying the functional protein unites will benefits to understand the molecular interactions of the virus, and then identify molecular targets for antiviral drug. Here, the comparative in-silico analysis of 33 coronavirus proteomes show that coronaviruses harbour diverse number of protein functional motifs. Coronaviruses harbour wide-range of motifs including those involved in integrin-binding and ESCRT pathway before virus budding. For example, SARS-CoV-2, but not SARS-CoV-1, encodes PPxY motif, which is required for virus entry and budding of HIV, influenza and adenoviruses. The quinolone inulding the antiviral FGI-104 is able to block ESCRT pathway and viral budding and has been used against HIV, HCV and Ebola virus.