ABSTRACT
Bauhinia variegata, a medicinal plant commonly known as Kachnar, belongs to the Leguminosae family. It is primarily found in tropical and warm regions around the world. It is known for its high pharmacological and commercial significance due to the presence of terpenoids, flavanoids, tannins, steroids, reducing sugars and cardiac glycosides, which aid in the cure of number of diseases. This study carried out profiling of Phytochemicals of this medicinal plant by using several in silico computational methodologies against SARS-CoV-2 virus. The 3D structure of Phytochemicals and the three target sites of the SARS-CoV-2 were constructed using Swiss-Model server and pre-processed in BIOVIA Discovery Studio followed by molecular docking carried on with Autodock tools-1.5.6. The pharmacokinetic and toxicological properties of these compounds were assessed using the Swiss ADME and admetSAR web servers, respectively. The potential toxicities generated by these compounds, as well as the energies of molecule-target interactions, hydrogen bonding, and hydrophobic interactions, were determined and analyzed. According to the findings, Phytochemicals such as Beta-sitosterol, Lupeol, Ombuin, and Quercetin exhibited higher binding affinity than the two reference drugs Ivermectin and Lopinavir, taken as comparison in the study. According to the preliminary results, these bioactive compounds exhibit the most promising docking scores with the three target sites of Corona virus. Hence, they could be regarded as prospective Phytochemicals found in Bauhinia variegata, potentially making this plant an active source of Phytochemicals required for the treatment of corona virus infections. Further experimental validation may necessitate the application of bioethics principles, laws, and regulations. Copyright © 2023 Ubiquity Press. All rights reserved.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 was originally identified in Wuhan city of China in December 2019 and it spread rapidly throughout the globe, causing a threat to human life. Since targeted therapies are deficient, scientists all over the world have an opportunity to develop novel drug therapies to combat COVID-19. After the declaration of a global medical emergency, it was established that the Food and Drug Administration (FDA) could permit the use of emergency testing, treatments, and vaccines to decrease suffering, and loss of life, and restore the nation's health and security. The FDA has approved the use of remdesivir and its analogs as an antiviral medication, to treat COVID-19. The primary protease of SARS-CoV-2, which has the potential to regulate coronavirus proliferation, has been a viable target for the discovery of medicines against SARS-CoV-2. The present research deals with the in silico technique to screen phytocompounds from a traditional medicinal plant, Bauhinia variegata for potential inhibitors of the SARS-CoV-2 main protease. Dried leaves of the plant B. variegata were used to prepare aqueous and methanol extract and the constituents were analyzed using the GC-MS technique. A total of 57 compounds were retrieved from the aqueous and methanol extract analysis. Among these, three lead compounds (2,5 dimethyl 1-H Pyrrole, 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide, and Benzonitrile m phenethyl) were shown to have the highest binding affinity (-5.719 to -5.580 kcal/mol) towards SARS-CoV-2 Mpro. The post MD simulation results also revealed the favorable confirmation and stability of the selected lead compounds with Mpro as per trajectory analysis. The Prime MM/GBSA binding free energy supports this finding, the top lead compound 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide showed high binding free energy (-64.377 ± 5.24 kcal/mol) towards Mpro which reflects the binding stability of the molecule with Mpro. The binding free energy of the complexes was strongly influenced by His, Gln, and Glu residues. All of the molecules chosen are found to have strong pharmacokinetic characteristics and show drug-likeness properties. The lead compounds present acute toxicity (LD50) values ranging from 670 mg/kg to 2500 mg/kg; with toxicity classifications of 4 and 5 classes. Thus, these compounds could behave as probable lead candidates for treatment against SARS-CoV-2. However further in vitro and in vivo studies are required for the development of medication against SARS-CoV-2.