Computational approach investigation bioactive molecules from Saussurea Costus plant as SARS-CoV-2 main protease inhibitors using reverse docking, molecular dynamics simulation, and pharmacokinetic ADMET parameters.

SARS-COV-2 virus causes (COVID-19) disease; it has become a global pandemic since 2019 and has negatively affected all aspects of human life. Scientists have made great efforts to find a reliable cure, vaccine, or treatment for this emerging disease. Efforts have been directed towards using medicinal plants as alternative medicines, as the active chemical compounds in them have been discovered as potential antiviral or anti-inflammatory agents. In this research, the potential of Saussurea costus (S. Costus) or QUST Al Hindi chemical consistent as potential antiviral agents was investigated by using computational methods such as Reverse Docking, ADMET, and Molecular Dynamics with different proteases COVID-19 such as PDB: 2GZ9; 6LU7; 7AOL, 6Y2E, 6Y84. The results of Reverse Docking the complex between 6LU7 proteases and Cynaropicrin compound being the best complex, as the same result, is achieved by molecular dynamics. Also, the toxicity testing result from ADMET method proved that the complex is the least toxic and the safest possible drug. In addition, 6LU7-Cynaropicrin complex obeyed Lipinski rule; it formed ≤5 H-bond donors and ≤10 H bond acceptors, MW < 500 Daltons, and octanol/water partition coefficient <5.

Computational approach investigation bioactive molecules from Saussurea Costus plant as SARS-CoV-2 main protease inhibitors using reverse docking, molecular dynamics simulation, and pharmacokinetic ADMET parameters

SARS-COV-2 virus causes (COVID-19) disease;it has become a global pandemic since 2019 and has negatively affected all aspects of human life. Scientists have made great efforts to find a reliable cure, vaccine, or treatment for this emerging disease. Efforts have been directed towards using medicinal plants as alternative medicines, as the active chemical compounds in them have been discovered as potential antiviral or anti-inflammatory agents. In this research, the potential of Saussurea costus (S. Costus) or QUST Al Hindi chemical consistent as potential antiviral agents was investigated by using computational methods such as Reverse Docking, ADMET, and Molecular Dynamics with different proteases COVID-19 such as PDB: 2GZ9;6LU7;7AOL, 6Y2E, 6Y84. The results of Reverse Docking the complex between 6LU7 proteases and Cynaropicrin compound being the best complex, as the same result, is achieved by molecular dynamics. Also, the toxicity testing result from ADMET method proved that the complex is the least toxic and the safest possible drug. In addition, 6LU7-Cynaropicrin complex obeyed Lipinski rule;it formed ≤5 H-bond donors and ≤10 H bond acceptors, MW < 500 Daltons, and octanol/water partition coefficient <5.

In silico detection of potential inhibitors from vitamins and their derivatives compounds against SARS-CoV-2 main protease by using molecular docking, molecular dynamic simulation and ADMET profiling.

COVID-19 is a new infectious disease caused by SARS-COV-2 virus of the coronavirus Family. The identification of drugs against this serious infection is a significant requirement due to the rapid rise in the positive cases and deaths around the world. With this concept, a molecular docking analysis for vitamins and their derivatives (28 molecules) with the active site of SARS-CoV-2 main protease was carried out. The results of molecular docking indicate that the structures with best binding energy in the binding site of the studied enzyme (lowest energy level) are observed for the compounds; Folacin, Riboflavin, and Phylloquinone oxide (Vitamin K1 oxide). A Molecular Dynamic simulation was carried out to study the binding stability for the selected vitamins with the active site of SARS-CoV-2 main protease enzyme. Molecular Dynamic shows that Phylloquinone oxide and Folacin are quite unstable in binding to SARS-CoV-2 main protease, while the Riboflavin is comparatively rigid. The higher fluctuations in Phylloquinone oxide and Folacin indicate that they may not fit very well into the binding site. As expected, the Phylloquinone oxide exhibits small number of H-bonds with protein and Folacin does not form a good interaction with protein. Riboflavin exhibits the highest number of Hydrogen bonds and forms consistent interactions with protein. Additionally, this molecule respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties which indicates that Riboflavin (Vitamin B2) could be interesting for the antiviral treatment of COVID-19.

Molecular docking, molecular dynamics simulation, and ADMET analysis of levamisole derivatives against the SARS-CoV-2 main protease (MPro).

Introduction: The new species of coronaviruses (CoVs), SARS-CoV-2, was reported as responsible for an outbreak of respiratory disease. Scientists and researchers are endeavoring to develop new approaches for the effective treatment against of the COVID-19 disease. There are no finally targeted antiviral agents able to inhibit the SARS-CoV-2 at present. Therefore, it is of interest to investigate the potential uses of levamisole derivatives, which are reported to be antiviral agents targeting the influenza virus. Methods: In the present study, 12 selected levamisole derivatives containing imidazo[2,1-b]thiazole were subjected to molecular docking in order to explore the binding mechanisms between these derivatives and the SARS-CoV-2 Mpro (PDB: 7BQY). The levamisole derivatives were evaluated for in silico ADMET properties for wet-lab applicability. Further, the stability of the best-docked complex was checked using molecular dynamics (MD) simulation at 20 ns. Results: Levamisole derivatives and especially molecule N°6 showed more promising docking results, presenting favorable binding interactions as well as better docking energy compared to chloroquine and mefloquine. The results of ADMET prediction and MD simulation support the potential of the molecule N°6 to be further developed as a novel inhibitor able to stop the newly emerged SARS-CoV-2. Conclusion: This research provided an effective first line in the rapid discovery of drug leads against the novel CoV (SARS-CoV-2).

Camphor, Artemisinin and Sumac Phytochemicals as inhibitors against COVID-19: Computational approach.

Covid-19 is an emerging infectious disease caused by coronavirus SARS-CoV-2. Due to the rapid rise in deaths resulted from this infection all around the world, the identification of drugs against this new coronavirus is an important requirement. Among the drugs that can fight this type of infection; natural products are substances that serve as sources of beneficial chemical molecules for the development of effective therapies. In this study, Camphor, Artemisinin and 14 Sumac phytochemicals were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). We have also performed molecular dynamic simulation at 100 ns with MM-GBSA/PBSA analysis for the structures with the best affinity in the binding site of the studied enzyme (Hinokiflavone and Myricetin) after docking calculations to consider parameters like RMSD, covariance, PCA, radius of gyration, potential energy, temperature and pressure. The result indicates that Hinokiflavone and Myricetin are the structures with best affinity and stability in the binding site of the studied enzyme and they respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties; so, these compounds have important pharmacokinetic properties and bioavailability, and they could have more potent antiviral treatment of COVID-19 than the other studied compounds.