Covalent drugs (i.e. compounds that form irreversible chemical bond with the protein receptor) have recently attracted attention of major pharmaceutical companies. In general, covalent drugs offer increased potency and long lasting action in comparison to their reversible analogues. However, screening covalent compounds using virtual docking methods, biochemical assays, and phenotypic screens represents a challenge because of the danger of non-specific covalent labeling of proteins with hyper reactive compounds. The second challenge is the synthesis of electrophilic compounds, which involves multiple synthetic steps which makes it difficult to create libraries of covalent drugs for screening and makes it difficult to conduct SAR. This invention addresses these challenges and reports the design algorithm of covalent compound libraries that do not cause the non-specific covalent labeling of proteins. The unique feature of the designed covalent compound libraries is that covalent electrophiles are derived either from natural products or from the known covalent drugs, and therefore are compatible with physiological conditions. Finally, this invention discloses the computer algorithm that allows creation of covalent compound libraries for virtual docking screens.