A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19

Coronavirus disease 2019 (COVID-19) is an inflammatory and infectious disease caused by severe acute respiratory syndrome coronavirus 2 virus with a complex pathophysiology. While COVID-19 vaccines and boosters are available, treatment of the disease is primarily supportive and symptomatic. Several research have suggested the potential of herbal medicines as an adjunctive treatment for the disease. A popular herbal medicine approved in the Philippines for the treatment of acute respiratory disease is Vitex negundo L. In fact, the Department of Science and Technology of the Philippines has funded a clinical trial to establish its potential as an adjunctive treatment for COVID-19. Here, we utilized network pharmacology and molecular docking in determining pivotal targets of Vitex negundo compounds against COVID-19. The results showed that significant targets of Vitex negundo compounds in COVID-19 are CSB, SERPINE1, and PLG which code for cathepsin B, plasminogen activator inhibitor-1, and plasminogen, respectively. Molecular docking revealed that α-terpinyl acetate and geranyl acetate have good binding affinity in cathepsin B; 6,7,4-trimethoxyflavanone, 5,6,7,8,3',4',5'-heptamethoxyflavone, artemetin, demethylnobiletin, gardenin A, geranyl acetate in plasminogen; and 7,8,4-trimethoxyflavanone in plasminogen activator inhibitor-1. While the results are promising, these are bound to the limitations of computational methods and further experimentation are needed to completely establish the molecular mechanisms of Vitex negundo against COVID-19.

In silico assessment of the binding of reported bioactive compounds from Phaseolus vulgaris L. (Fabaceae) towards the wild-type and mutant estrogen receptor-alpha

Background@#Breast cancer is one of the leading causes of deaths in women worldwide, affecting nearly 7.8 million people. In 2020 in the Philippines, there were around 150,000 Filipinos who were newly diagnosed with the disease. The complex pathogenesis of breast cancer in addition to the emergence of resistance to therapy makes the treatment very challenging. Compounds that can antagonize the effects of estradiol towards ER-α, especially the mutant Y537S type are sought for. @*Objectives@#The focus of this study was the in-silico assessment of the reported secondary metabolites from Phaseolus vulgaris L. (fam. Fabaceae) towards the wild-type and mutant ER-α. Bioisosteric replacement was conducted to generate analogs that can possibly have a comparable binding affinity as estradiol towards estrogen receptors alpha. @*Results@#Majority of the secondary metabolites present in Phaseolus vulgaris L. belong to the group of phytoestrogens, phytosterols, and plant hormones. These groups of compounds exhibited favorable binding energies toward the wild-type and mutant (Y537S) estrogen receptors alpha. Moreover, they bind to the same ligand binding pocket as estradiol, involving similar interactions and amino acid residues. @*Conclusion@#Compounds from Phaseolus vulgaris L. can potentially target ER-α. Four gibberellin A19 analogs were generated that exhibited favorable binding towards the wild- and mutant- ER-α and may be further optimized to obtain a promisin gcompound against breast cancer.