A scary viral pneumonia (COVID-19) has recently engulfed the globe. The new strain of the virus, named SARS-CoV-2, belongs to the coronavirus family, so research aims to screen multimodal structure-based structure-design of ligands and drugs and then docked to the main viral protease to investigate the active binding sites. A new 3-acetyl-7-hydroxy coumarin (HL) and its Cu(II), Ni(II), Zn(II), and Mn(II) complexes have been formed and characterized by elemental analysis, IR, 1H NMR, and UV visible spectra, as well as magnetic and thermal measurements. Molar conductance experiments have shown that all complexes are non-ionic or non-electrolytes. IR spectra show that the ligand (HL) behaves as a bidentate monobasic ligand coordinating via the oxygen atom of the deprotonated phenolic -OH group and the nitrogen atom of the azo group (-N=N-), forming a six-member chelating ring. The molecular and electronic structures of the investigated compounds were also analyzed using quantum chemical calculations. The complexes’ thermal decomposition exposed the outer and inner water molecules as well as the end product, which is mainly metal oxide. The thermodynamic parameter ligand (HL) and its metal complexes are calculated using the Coats-Redfern and Horowitz Metzger methods. Using absorption spectra, the ligand (HL) binding behavior of the calf thymus DNA and its metal complexes were studied. A molecular docking simulation computational method is performed to screen the antiviral activity of drugs, natural drug activity, sources, and anti-SARS-CoV-2 genome inhibitory compounds. The primary virus protease collected from a Bank of Protein Data (PDB# 6YB7) and docked with a sequence of HL and its complexes. On the other hand, the prediction of binding between azo compound with the breast cancer receptor 3hb5-oxidoreductase and the prostate cancer mutant 2q7k – hormone was also made. The docking results were promised and indicated that the reported ligand can firmly bind to the SARS-CoV-2, breast, and prostate cancer leads to inhibition of its infectious impact. The cytotoxic activity of ligand (HL) and its metal complexes was tested against human cancer MCF-7 (breast cancer).