Investigation of berberine and its derivatives in Sars Cov-2 main protease structure by molecular docking, PROTOX-II and ADMET methods: in machine learning and in silico study

Bioactive compounds found in plants also have pharmacological antiviral effects. Berberine (BBR), an alkaloid found naturally in plants, is one of the phytochemicals with a wide range of biological activities, including antiviral, anticancer, anti-inflammatory and anti-inflammatory. In this study, we firstly aimed to predict pIC50 values for selcted compounds and then extract the binding patterns of berberine and its derivatives in the Sars Cov-2 Master Protease structure via employing molecular docking approache. Our results showed that berberine and its derivatives have good binding affinities towared Sars Cov2 main protease protein. Based on docking results the pharamaccokinetic studies for berberine, berberrubine, demethylen-berberine, jatrorrhizin, and thalifendine, were conducted and showed a good pharamacokinetic properties as an oral drugs. For deep inspection, we utiilized molecular dynmaics simulation to examine the Sars Cov2 main protease-ligand stabilities. The molecular dynamics simulation and PCA investigations revealed that thalifendine have a strong willing to act as good bindinder to SARS-CoV-2 protease. Further, the network based pharamacology showed that these drugs mediate different pathways such as human T-cell leukemia virus 1 infection, viral carcinogenesis, human immunodeficiency virus 1 infection, kaposi sarcoma-associated herpesvirus infection and epstein-Barr virus infection.The findings of this study have an important recomendation for thalifendine for more in vivo and in vitro studies to work. Communicated by Ramaswamy H. Sarma

Automated summary

Bioactive compounds found in plants, such as berberine, have shown promising antiviral effects against SARS-CoV-2. This study investigated the binding affinities and pharmacokinetic properties of berberine and its derivatives, and found that they have strong binding to the main protease protein of SARS-CoV-2. Molecular dynamics simulation revealed that thalifendine exhibits excellent stability in complex with the protease. Network pharmacology analysis further demonstrated that these compounds can modulate various pathways related to viral infections. These findings highlight the potential of thalifendine for further in vivo and in vitro studies.