In this work, we describe a simple and easy synthetic approach to variously 4-aryl-2-alkylphosphonomethyl-4-oxobutanenitrile based on the reaction of aromatic aldehydes with phosphorylated Michael’s acceptors in good yields. A general mechanism for the reactions was also proposed. Characterization of the products was carried out by several spectroscopic tools, including Infrared and Nuclear Magnetic Resonance Spectroscopies (1H, 13C, and 31P-NMR). Molecular docking studies were conducted on the synthesized materials against (1UK4) the crystal structure of the SARS Coronavirus Main Proteinase (3CLpro) to study the antiviral activity of these compounds and against (1E3K) the Human Progesterone Receptor to study the anticancer activity of these compounds. We found that compound (5i) was the best one in both antiviral and anticancer activity (according to the binding energy values).