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 17 β -glucosyl and carboxylic 3 α -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. Graphical abstract Image 1 Highlights • Calendulaglycoside A (5) achieved a superior binding than the co-crystallized inhibitor towards the M pro of SARS-CoV-2. • Structural preferentiality for triterpene-M pro binding highlights the significant role of 17 β -glucosyl and carboxylic 3 α -galactosyl I moieties through high electrostatic interactions. • This study clarified a promising SAR responsible for the antiviral activity against the SARS-CoV-2 M pro .
【저자키워드】 COVID-19, triterpenes, SAR, computational studies, C. officinalis L., 【초록키워드】 Treatment, SARS-CoV-2, pandemic, severity, drug, antiviral activity, MD simulation, Health, stability, therapeutic, inhibitor, binding, compounds, electrostatic interactions, Image, Safe, Trajectories, Abstract, Molecular docking study, Compound, M pro, inhibitory activity, molecular docking studies, electrostatic interaction, effective, highlight, N3 inhibitor, Course, intrinsic, Result, responsible, caused, investigated, clinically, was performed, inhibiting, binding score, co-crystallized, co-crystallized N3 inhibitor, drug candidates targeting, the SARS-CoV-2, treatment for COVID-19, 【제목키워드】 SARS-CoV-2, docking, molecular,