New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

Seliem, Israa A.; Girgis, Adel S.; Moatasim, Yassmin; Kandeil, Ahmed; Mostafa, Ahmed; Ali, Mohamed A.; Bekheit, Mohamed S.; Panda, Siva S.

Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). We have developed a set of pyrazine‐based small molecules. A series of pyrazine conjugates was synthesized by microwave‐assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR‐CoV‐2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine‐triazole conjugates (5 d–g) and (S)‐N‐(1‐(benzo[d]thiazol‐2‐yl)‐2‐phenylethyl)pyrazine‐2‐carboxamide 12 i 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).