Department of Chemistry, ARSD College, University of Delhi, New Delhi, India.
Department of Chemistry, Maitreyi College, University of Delhi, New Delhi, India.
Chem Biodivers. 2024 Oct;21(10):e202400904. doi: 10.1002/cbdv.202400904. Epub 2024 Sep 11.
There was an emergency call globally when COVID-19 was detected in December 2019. The SARS-CoV-2 virus, a modified virus, causes this contagious disease. Although research is being conducted throughout the world, the main target is still to find the promising candidate to target RNA-dependent RNA polymerase (RdRp) to provide possible drug against COVID-19. Aim of this work is to find a molecule to inhibit the translational process of viral protein synthesis. Density Functional Theory calculations revealed information about the formation of the desired ligand (RD). Molecular docking of RD with RdRp was performed and compared with some reported molecules and the data revealed that RD had the best docking score with RdRp (-6.7 kcal/mol). Further, molecular dynamics (MD) simulations of RD with RdRp of SARS-CoV-2 revealed the formation of stable complex with a maximum number of seven hydrogen bonds. Root mean square deviations values are in acceptable range and root mean square fluctuations are also low, indicating stable complex formation. Further, based on MM-GBSA calculation, RD formed a stable complex with RdRp of nCoV with ΔG° of -12.28 kcal mol.
2019 年 12 月检测到 COVID-19 时，全球出现了紧急呼叫。这种传染性疾病是由 SARS-CoV-2 病毒（一种改良病毒）引起的。尽管全世界都在进行研究，但主要目标仍然是找到有前途的候选药物，以针对 RNA 依赖性 RNA 聚合酶（RdRp），提供可能对抗 COVID-19 的药物。这项工作的目的是找到一种抑制病毒蛋白合成翻译过程的分子。密度泛函理论计算揭示了形成所需配体（RD）的信息。对 RD 与 RdRp 的分子对接进行了研究，并与一些报道的分子进行了比较，数据表明 RD 与 RdRp 的对接评分最佳（-6.7 kcal/mol）。此外，对 SARS-CoV-2 的 RdRp 进行的 RD 的分子动力学（MD）模拟显示，形成了具有最大数量为七个氢键的稳定复合物。均方根偏差值在可接受范围内，均方根波动也较低，表明形成了稳定的复合物。此外，基于 MM-GBSA 计算，RD 与 nCoV 的 RdRp 形成了稳定的复合物，ΔG°为-12.28 kcal/mol。
