Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-basedsmall molecules. A series of pyrazine conjugates synthesized by microwave-assisted click chemistry and benzotriazole chemistry.All the synthesized conjugates were screened against the SAR-CoV-2 virus and determined their cytotoxicity. Computational studies were carried out to validate the biological data. Compounds 5d-g and 12i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).