Synthesis and SARS-CoV-2 3CL Protease Inhibitory Effects of Oxazolidinone Derivatives

Abstract

The 3-chymotrypsin-like protease (3CLpro) is an attractive target for the development of anti- SARS (severe acute respiratory syndrome) drugs. In this work, a series of oxazolidinone derivatives 3a-3v were synthesized and their inhibitory activities against SARS coronavirus 2 (SARS-CoV-2) 3CLpro were evaluated by the fluorescence resonance energy transfer (FRET)-based enzymatic assay. Among synthesized compounds, 3g displayed the best inhibitory activity, with a half maximal inhibitory concentration (IC50) value of 14.47 μM. Also, docking studies implied that compound 3g was fitted into the active pocket of 3CLpro, forming a hydrogen bond with Glu166.

Oxazolidinones Antibiotics, Chemistry, Applications and Role in COVID-19 Treatment

“…Nelson et al proved their hypothesis which believed that the role of LNZ may be due to an interaction between (R and S)-linezolid with receptor-binding domain (RBD) of SARS-CoV-2 spike protein complexed with human angiotensin converting enzyme2 (ACE2). This opinion was proven using electronic and molecular docking [17]. Shengxian Zhao et al were synthesized 22 compounds of oxazolidinones derivatives (3a-3v) and screened them.…”

“…They found that compound 3 g displayed the most potent inhibitory activity with an IC 50 value of 14.47 μmol·L −1 . Molecular docking analysis showed the modes of action of compound 3 g with 3-chymotrypsin-like protease (3CLpro) which responsible for cutting at least 11 sites and is extremely important for coronavirus replication [17]. Therefore, 3CLpro is an ideal target for the development of anti-coronavirus drug [17].…”

“…Molecular docking analysis showed the modes of action of compound 3 g with 3-chymotrypsin-like protease (3CLpro) which responsible for cutting at least 11 sites and is extremely important for coronavirus replication [17]. Therefore, 3CLpro is an ideal target for the development of anti-coronavirus drug [17]. Clinical applications showed that LNZ was a good antibiotic in treatment of nosocomial infections in COVID- clinical and microbiological efficacy in COVID-19 patients who were suffering from bacterial pneumonia received intravenous dose of 600 mg of linezolid every 12 hours for 7 to 10 days and all patients recovered and discharged from hospital.…”