Arjunetin as a promising drug candidate against SARS-CoV-2: molecular dynamics simulation studies

Abstract

Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1 H, 13 C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma

Medical Plants and Natural Compounds as Anti-Viral Agents: Present and Future Trends

“…seeds. It showed a moderate anti-HIV protease effect [94][95][96][97][98][99][100][101][102][103][104][105]. In view of the signification number of plant extracts that have yielded positive results it seems reasonable to conclude that there are probably numerous kinds of antiviral agents in these materials.…”

“…seeds. It showed a moderate anti-HIV protease effect[94][95][96][97][98][99][100][101][102][103][104][105].2.78. Pomolic Acid Phitolic AcidSome triterpenes as Ursonic acid, Hydroxyhopanone were identified of Balanocarpus heimii King.…”

“…seeds. It showed a moderate anti-HIV protease effect[94][95][96][97][98][99][100][101][102][103][104][105].…”

Significant perspectives on various viral infections targeted antiviral drugs and vaccines including COVID-19 pandemicity

“…In fact, thalidomide has an anti-inflammatory activity caused by its potential rapidity of the mRNA deficiency within blood cell, decrease the tumor necrosis factor-alpha (TNFα), enhance the interleukins secretion as represented as IL-12, and triggering usual killer cells. Senthil et al concluded that Arjunetin acts an efficient protease inhibitor of SARS-CoV-2 that is comparable to Lopinavir and Remdesivir antivirals [89][90][91] and also assisting as a drug aspirant against SARS-CoV-2 (Fig. 9f ).…”