Abstract
Despite the effectiveness of COVID-19 vaccines, there is still an urgent need for discovering new anti-viral drugs to address the awful spread and transmission of the rapidly modifiable virus. In this study, the ability of a small library of enantiomerically pure spirooxindolopyrrolidine-grafted piperidones to inhibit the main protease of SARS-CoV-2 (M pro ) is evaluated. These spiroheterocycles were synthesized by 1,3-dipolar cycloaddition of various stabilized azomethine ylides with chiral dipolarophiles derived from N- [ (S) -(-)-methylbenzyl]-4-piperidone. The absolute configuration of contiguous carbons was confirmed by a single crystal X-ray diffraction analysis. The binding of these compounds to SARS-CoV-2 M pro was investigated using molecular docking and molecular dynamics simulation. Three compounds 4a , 4b and 4e exhibited stable binding modes interacting with the key subsites of the substrate-binding pocket of SARS-CoV-2 M pro . The synthesized compounds represent potential leads for the development of novel inhibitors of SARS-CoV-2 main protease protein for COVID-19 treatment.
Keywords: Hirshfeld analysis; SARS-CoV-2; crystal structure; enantiopure spirooxindolopyrrolidine-piperidones; molecular docking; molecular dynamics.
【저자키워드】 SARS-CoV-2, molecular docking, molecular dynamics., crystal structure, Hirshfeld analysis, enantiopure spirooxindolopyrrolidine-piperidones, 【초록키워드】 COVID-19, Treatment, molecular docking, Transmission, molecular dynamics, protease, virus, Molecular dynamics simulation, COVID-19 treatment, Spread, Protein, COVID-19 vaccines, Effectiveness, molecular, crystal structure, anti-viral drug, binding, Analysis, X-ray diffraction, inhibitors of SARS-CoV-2, Compound, M pro, these compounds, investigated, inhibit, evaluated, exhibited, these compound, binding mode, 【제목키워드】 Structure, novel, synthesis, candidate, crystal,