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

ABSTRACT: 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.

SUBMITTER: Belhassan A

PROVIDER: S-EPMC8354799 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Belhassan Assia A Zaki Hanane H Chtita Samir S Alaqarbeh Marwa M Alsakhen Nada N Benlyas Mohamed M Lakhlifi Tahar T Bouachrine Mohammed M

Computers in biology and medicine 20210811

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 ...[more]

PMID: 34411900

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Project description:BackgroundA recent COVID-19 pandemic has resulted in a large death toll rate globally and even no cure or vaccine has been successfully employed to combat this disease. Patients have been reported with multi-organ dysfunction along with acute respiratory distress syndrome which implies a critical situation for patients and made them difficult to breathe and survive. Moreover, pathology of COVID-19 is also related to cytokine storm which indicates the elevated levels of interleukin (IL)-1, IL-6, IL-12, and IL-18 along with tumor necrosis factor (TNF)-α. Among them, the proinflammatory cytokine IL-6 has been reported to be induced via binding of severe acute respiratory syndrome coronavirus 2 (SARS)-CoV-2 to the host receptors.MethodologyInterleukin-6 blockade has been proposed to constitute novel therapeutics against COVID-19. Thus, in this study, 15 phytocompounds with known antiviral activity have been subjected to test for their inhibitory effect on IL-6. Based on the affinity prediction, top 3 compounds (isoorientin, lupeol, and andrographolide) with best scores were selected for 50 ns molecular dynamics simulation and MMGB/PBSA binding free energy analysis.ResultsThree phytocompounds including isoorientin, lupeol, and andrographolide have shown strong interactions with the targeted protein IL-6 with least binding energies (-7.1 to -7.7 kcal/mol). Drug-likeness and ADMET profiles of prioritized phytocompounds are also very prominsing and can be further tested to be potential IL-6 blockers and thus benficial for COVID-19 treatment. The moelcular dynamics simulation couple with MMGB/PBSA binding free energy estimation validated conformational stability of the ligands and stronger intermolecular binding. The mean RMSD of the complexes is as: IL6-isoorientin complex (3.97 Å ± 0.77), IL6-lupeol (3.97 Å ± 0.76), and IL6-andrographolide complex (3.96 Å ± 0.77). In addition, the stability observation was affirmed by compounds mean RMSD: isoorientin (0.72 Å ± 0.32), lupeol (mean 0.38 Å ± 0.08), and andrographolide (1.09 Å ± 0.49). A similar strong agreement on systems stability was unraveled by MMGB/PBSA that found net binding net ~ -20 kcal/mol for the complexes dominated by van der Waal interaction energy.ConclusionIt has been predicted that proposing potential IL-6 inhibitors with less side effects can help critical COVID-19 patients because it may control the cytokine storm, a major responsible factor of its pathogenesis. In this study, 3 potential phytocompounds have been proposed to have inhibitory effect on IL-6 that can be tested as potential therapeutic options against SARS-CoV-2.

Project description:BackgroundThe sanitary emergency installed in the world, generated by the pandemic of COVID-19, instigates the search for scientific strategies to mitigate the damage caused by the disease to different sectors of society. The disease caused by the coronavirus, SARS-CoV-2, reached 216 countries/territories, where about 199 million people were reported with the infection. Of these, more than 4 million died. In this sense, strategies involving the development of new antiviral molecules are extremely important. The main protease (Mpro) from SARS-CoV-2 is an important target, which has been widely studied for antiviral treatment. This work aims to perform a screening of pharmacodynamics and pharmacokinetics of synthetic hybrids from thymoquinone and artemisin (THY-ART) against COVID-19.ResultsMolecular docking studies indicated that hybrids of artemisinin and thymoquinone showed a relevant interaction with the active fraction of the enzyme Mpro, when compared to the reference drugs. Furthermore, hybrids show an improvement in the interaction of substances with the enzyme, mainly due to the higher frequency of interactions with the Thr199 residue. ADMET studies indicated that hybrids tend to permeate biological membranes, allowing good human intestinal absorption, with low partition to the central nervous system, potentiation for CYP-450 enzyme inhibitors, low risk of toxicity compared to commercially available drugs, considering mainly mutagenicity and cardiotoxicity, low capacity of hybrids to permeate the blood-brain barrier, high absorption and moderate permeability in Caco-2 cells. In addition, T1-T7 tend to have a better distribution of their available fractions to carry out diffusion and transport across cell membranes, as well as increase the energy of interaction with the SARS-CoV-2 target.ConclusionsHybrid products of artemisinin and thymoquinone have the potential to inhibit Mpro, with desirable pharmacokinetic and toxicity characteristics compared to commercially available drugs, being indicated for preclinical and subsequent clinical studies against SARS-CoV-2. Emphasizing the possibility of synergistic use with currently used drugs in order to increase half-life and generate a possible synergistic effect. This work represents an important step for the development of specific drugs against COVID-19.

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

Publications

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

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