Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamics simulations

Seshu Vardhan ； Suban K. Sahoo

《Journal of Traditional and Complementary Medicine》 12卷1期 (2022/01) Pp. 44-54

https://doi.org/10.1016/j.jtcme.2021.12.002

摘要

Background and aim: The ongoing global pandemic due to SARS-CoV-2 caused a medical emergency. Since December 2019, the COVID-19 disease is spread across the globe through physical contact and respiratory droplets. Coronavirus caused a severe effect on the human immune system where some of the non-structural proteins (nsp) are involved in virus-mediated immune response and pathogenesis. To suppress the viral RNA replication mechanism and immune-mediated responses, we aimed to identify limonoids and triterpenoids as antagonists by targeting helicases (nsp13), exonuclease (nsp14), and endoribonuclease (nsp15) of SARS-CoV-2 as therapeutic proteins. Experimental procedure: In silico molecular docking and drug-likeness of a library of 369 phytochemicals from limonoids and triterpenoids were performed to screen the potential hits that binds effectively at the active site of the proteins target. In addition, the molecular dynamics simulations of the proteins and their complexes with the potential hits were performed for 100 ns by using GROMACS. Results and conclusion: The potential compounds 26-deoxyactein and 25-O-anhydrocimigenol 3-O-beta-D-xylopyranoside posing strong interactions with a minimum binding energy of -10.1 and -9.5 kcal/mol, respectively and sustained close contact with nsp13 for 100 ns. The nsp14 replication fork activity was hindered by the tomentosolic acid, timosaponin A-I, and shizukaol A with the binding affinity score of -9.2, -9.2, and -9.0 kcal/mol, respectively. The nsp15 endoribonuclease catalytic residues were inhibited potentially by limonin, 25-O-anhydrocimigenol 3-O-alpha-L-arabinopyranoside, and asperagenin posing strong binding affinity scores of -9.0, -8.8, and -8.7 kcal/mol, respectively. Computationally predicted potential phytochemicals for SARS-CoV-2 are known to possess various medicinal properties.

關鍵字

COVID-19 ； Limonoids ； Triterpenoids ； Molecular docking ； Dynamics simulation

參考文獻

Fuzimoto A, Isidoro C. The antiviral and coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - additional weapons in the fight against the COVID-19 pandemic? J Tradit Complement Med. 2020;10(4):405-419. https://doi.org/10.1016/j.jtcme.2020.05.003

Vidoni C, Fuzimoto A, Ferraresi A, Isidoro C. Targeting autophagy with natural products to prevent SARS-CoV-2 infection. J Tradit Complement Med. 2021. https://doi.org/10.1016/j.jtcme.2021.10.003

Vardhan S, Sahoo S. Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV2 virus into human host cells. J Tradit Complement Med. 2021. https://doi.org/10.1016/j.jtcme.2021.04.001

Abhilash K. Second wave of COVID-19: unrelenting rampage of the SARS CoV-2 variants. Curr Med Issues. 2021;19(3):129. https://doi.org/10.4103/cmi.cmi_44_21

Pal M, Berhanu G, Desalegn C, Kandi V. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus. 2020;12(3), e7423. https://doi.org/10.7759/cureus.7423