Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies

Background and aim: The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, natural products can provide therapeutic alternatives that could be employed as an effective safe treatment for COVID-19. Experimental procedure: Twelve compounds were isolated from the aerial parts of C. officinalis L. and investigated for their inhibitory activities against SARS-CoV-2 M^(pro) compared to its co-crystallized N3 inhibitor using molecular docking studies. Furthermore, a 100 ns MD simulation was performed for the most active two promising compounds, Calendulaglycoside A (SAP5) and Osteosaponin-I (SAP8). Results and conclusion: At first, molecular docking studies showed interesting binding scores as compared to the N3 inhibitor. Calendulaglycoside A (SAP5) achieved a superior binding than the co-crystallized inhibitor indicating promising affinity and intrinsic activity towards the M^(pro) of SARS-CoV-2 as well. Moreover, findings illustrated preferential stability for SAP5 within the M^(pro) pocket over that of N3 beyond the 40 ns MD simulation course. Structural preferentiality for triterpene-M^(pro) binding highlights the significant role of 17β-glucosyl and carboxylic 3α-galactosyl I moieties through high electrostatic interactions across the MD simulation trajectories. Furthermore, this study clarified a promising SAR responsible for the antiviral activity against the SARS-CoV-2 M^(pro) and the design of new drug candidates targeting it as well. The above findings could be promising for fast examining the previously isolated triterpenes both pre-clinically and clinically for the treatment of COVID-19.

關鍵字

COVID-19 ； C. officinalis L. ； Triterpenes ； Computational studies ； SAR

參考文獻

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被引用紀錄

Isidoro, C., Chang, A. C. F., & Sheen, L. Y. (2022). Natural products as a source of novel drugs for treating SARS-CoV2 infection. Journal of Traditional and Complementary Medicine, 12(1), 1-5. https://doi.org/10.1016/j.jtcme.2022.02.001

Singh, R., Bhardwaj, V. K., Sharma, J., Purohit, R., & Kumar, S. (2022). In-silico evaluation of bioactive compounds from tea as potential SARS-CoV-2 nonstructural protein 16 inhibitors. Journal of Traditional and Complementary Medicine, 12(1), 35-43. https://doi.org/10.1016/j.jtcme.2021.05.005

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Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies

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