Molecular recognition of bio-active triterpenoids from Swertia chirayita towards hepatitis Delta antigen: a mechanism through docking, dynamics simulation, Gibbs free energy landscape.

Medicinal plants the underpinning of indigenous herbal serve, are the possible source of key compounds for the development of new drugs. Hepatitis D, one of the most widespread infectious diseases associated with global public health issues. Therefore, we aim to screen natural compounds to find out potent inhibitor towards hepatitis delta antigen. Through ADMET investigation, we have screened twenty phytochemicals for this study. Additionally, using molecular docking, these phytochemicals were docked with the HDV protease which signifies the phytochemicals beta-amyrin, chiratenol, episwertenol and swertanone have a significant capability to bind with hepatitis D virus protein. The docking study was further accompanied by analyzes RMSD, RMSF, Rg, SASA, Hbond number, and principal component analysis through 100 ns MD simulations. Based on our principal component analysis, beta-amyrin, chiratenol, episwertenol and swertanone phytochemicals can be a potential drug candidates for inhibition of hepatitis D. The above observation is also supported by our Gibbs free energy landscape study. The potential therapeutic characteristics of the phytochemicals against hepatitis D inhibition offer additional support for the in vitro and in vivo studies in future.

Identification of phytochemicals from Eclipta alba and assess their potentiality against Hepatitis C virus envelope glycoprotein: virtual screening, docking, and molecular dynamics simulation study.

Hepatitis C virus has a major role in spreading chronic liver disease and hepatocellular carcinoma. Factors such as high costs, pharmacological side effects, and the development of drug resistance strains require the development of new and potentially effective antiviral to treat the various stages of Hepatitis C. Bioactive chemicals have been extracted from medicinal plants and are utilized by humans for the goal of maintaining a healthy lifestyle. The goal of this work is to recognize phytochemicals from Eclipta alba and assess their potentiality activity against the hepatitis C virus envelope glycoprotein using in silico approaches. Phytochemicals from Eclipta alba were virtually screened by Auto dock raccoon and 12 compounds were selected for molecular docking to probe the active binding site. The top two compounds based on the binding score like ecliptalbine and oleanolic acid with HCV E2 glycoprotein exhibit binding energy -8.88 and -8.02 kcal/mol, respectively. The chemicals' usefulness was reinforced by positive pharmacokinetic data. The phytocompounds were identified as potent HCV inhibitors based on the drug likeness and ADMET properties. Both ecliptalbine and oleanolic acid underwent molecular dynamics simulations to determine features such as RMSD, RMSF, SASA, hydrogen-bond number, and MM-PBSA-based binding free energy. From the molecular docking and molecular dynamics simulation study revealed that oleanolic acid obtained from Eclipta alba can be used as inhibitors against Hepatitis C. The identified inhibitor from our study will be study in vitro and in vivo studies to check their efficacy against Hepatitis C.Communicated by Ramaswamy H. Sarma.

Bioactive compounds from Pandanous fascicularis as potential therapeutic candidate to tackle hepatitis a inhibition: Docking and molecular dynamics simulation study.

Due to extensive pharmacological research, medicinal plants the underpinning of indigenous herbal serve as a possible source of key compounds for the development of new drugs. Hepatitis A, one of the most widespread infectious diseases associated with global public health issues. The transmission of hepatitis A virus (HAV) occurs, through personal contact, as well as contaminated food/water. The HAV 3C cysteine protease is a non-structural protein, plays pivotal role in proliferation and viral replication. Significant phytochemicals of Pandanous fascicularis include phytosterol, kobusin, epipinoresinol, and ceroptene, which have a wide variety of biological functions. Through ADMET investigation, we have screened fifteen phytochemicals for this study. Additionally, using molecular docking, these phytochemicals were docked with the HAV 3C protease which signifies the phytochemicals phytosterol, kobusin, epipinoresinol, and ceroptene have a significant capability to bind with hepatitis A virus protein.The docking study was further accompanied by analyzes RMSD, RMSF, Rg, SASA, H-bond number, and principal component analysis through 100 ns MD simulations. The molecular dynamics study reveals that, all four phytochemicals possess considerable binding efficacy with hepatitis A virus protein. Based on our computational study and MMGBSA calculations, phytosterol, kobusin and epipinoresinol phytochemicals may be a potential drug candidate for inhibition of hepatitis A. The potential therapeutic characteristics of the phytochemicals against hepatitis A inhibition offer additional support for the in vitro and in vivo studies in future.Communicated by Ramaswamy H. Sarma.

Computational study to evaluate the potency of phytochemicals in Boerhavia diffusa and the impact of point mutation on cyclin-dependent kinase 2-associated protein 1.

A protein's function is closely related to its structural properties. Mutations can affect the functionality of a protein. Different cancer tissues have found disordered expression of the cyclin-dependent kinase 2-associated Protein 1 (CDK2AP1) gene. A protein molecule's conformational flexibility affects its interaction with phytochemicals and their biological partners at various levels. Boerhavia diffusa has been investigated most extensively for its medicinal activities like anticancer properties. It contains many bioactive compounds like Boeravinone A, Boeravinone B, Boeravinone C, Boeravinone D, Boeravinone E, Boeravinone F, Boeravinone G, Boeravinone H, Boeravinone I and Boeravinone J. We have studied to analyse the binding efficacy properties as well as essential dynamic behaviour, free energy landscape of both the native and mutant protein CDK2AP1 with bioactive compounds from Boerhavia diffusa plant extracts through computational approaches by homology modelling, docking and molecular dynamics simulation. From the molecular docking study, we found that. Boeravinone J have best binding affinity (-7.9 kcal/mol) towards the native protein of CDKAP1 compared to others phytochemicals. However, we found the binding energy for H23R and C105R (mutation point) -7.8 and -7.6 kcal/mol, respectively. A single minima energy point (from 100 ns molecular dynamics simulation study) was found in the H23R mutant with Boeravinone J complex suggested that minimum structural changes with less conformational mobility compared C105A mutant model.Communicated by Ramaswamy H. Sarma.