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The novel coronavirus SARS-CoV-2 (COVID-19) is a member of the family Coronaviridae and contains ssRNA genome. The emergency of COVID-19 has caused global threatened and panic health security. In order to detect common regions and genes of the Severe acute respiratory syndrome-associated coronavirus 2, we collected the whole genome of all viruses available in databases for this family (55 complete genomes), and made comparative genomic analyses with the collected data. We performed an interactomics approach to identify miRNAs that could be affected in some regions of the whole virus genome. As well as, protein structure modeling was used for modeling of related sequence. Cladogram revealed Bat coronavirus, MERS-related coronavirus, SARS-related coronavirus and SARS coronavirus 2 are closely related. The most important genes involved in the disease were RELA in virus genome and ACE2 receptors and CLEC4M genes in the host genome. RELA gene was suppressed by hsa-miR-516b-3p, hsa-miR-3529-3p and hsa-miR-6749-3p, ACE2 receptor was suppressed by hsa-miR-23b-5p and hsa-miR-769-5p, and finally, hsa-miR-4462 and hsa-miR-5187-5p suppressed CLEC4M gene. Therefore, our results will help to control and treat COVID-19 and revealed new insight into the vaccine design and miRNA therapy. *Correspondence to: A. Bahrami, Department of Animal Science, University of Tehran, Karaj, I.R. Iran, Tel: +98 9199300065; E-mail: a.bahrami@ut.ac.ir

Comparative genomics identifies key genes and miRNAs that may be used as a strategy to control and treatment of COVID-19