Background: The SARS-CoV-2 virus is a new highly contagious Coronavirus with a positive-sense RNA encoding 16 non-structural proteins (nsps16, nsp15, nsp3). In this study, the coronavirus pathogenicity and the losartan functional ligand for inhibiting TRPM2 and macrodomain have been molecularly evaluated.Material and method: In this study, the structures of macrodomain binding ADP ribose in CoVs and human Transient Receptor Potential Cation Channel Subfamily M Member 2 (TRPM2) protein were downloaded from protein data bank. Then, a virtual screening was done to recognize the hit compounds from GalaXi_2019-10, KnowledgeSpace_2019-05, and REALspace_2019-12 databases. This collection, then, was imported to the ligandScout software, on the base of Adenosine Diphosphate Ribose (ADPR) pharmacophore model. Result: Among seven compounds, five compounds were finally evaluated as the structural analogs of ADPR or other nucleotides, from which one compound was a non-FDA-approved sulphonamide and was removed. The other compound, losartan, was finally selected for molecular docking and molecular dynamic simulation. According to the virtual screening and docking, losartan was candidate as an effective ligand for TRPM2 and macrodomain. Conclusion: In the current study losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. The inhibitory effect of losartan on PARP has been shown and it could interfere positively in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress and apoptosis in COVID-19.