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Sci Rep ; 12(1): 11120, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-2028700


The latest coronavirus pandemic (SARS-CoV-2) poses an exceptional threat to human health and society worldwide. The coronavirus (SARS-CoV-2) spike (S) protein, which is required for viral-host cell penetration, might be considered a promising and suitable target for treatment. In this study, we utilized the nonalkaloid fraction of the medicinal plant Rhazya stricta to computationally investigate its antiviral activity against SARS-CoV-2. Molecular docking and molecular dynamics simulations were the main tools used to examine the binding interactions of the compounds isolated by HPLC analysis. Ceftazidime was utilized as a reference control, which showed high potency against the SARS-CoV-2 receptor binding domain (RBD) in an in vitro study. The five compounds (CID:1, CID:2, CID:3, CID:4, and CID:5) exhibited remarkable binding affinities (CID:1, - 8.9; CID:2, - 8.7; and CID:3, 4, and 5, - 8.5 kcal/mol) compared to the control compound (- 6.2 kcal/mol). MD simulations over a period of 200 ns further corroborated that certain interactions occurred with the five compounds and the nonalkaloidal compounds retained their positions within the RBD active site. CID:2, CID:4, and CID:5 demonstrated high stability and less variance, while CID:1 and CID:3 were less stable than ceftazidime. The average number of hydrogen bonds formed per timeframe by CID:1, CID:2, CID:3, and CID:5 (0.914, 0.451, 1.566, and 1.755, respectively) were greater than that formed by ceftazidime (0.317). The total binding free energy calculations revealed that the five compounds interacted more strongly within RBD residues (CID:1 = - 68.8, CID:2 = - 71.6, CID:3 = - 74.9, CID:4 = - 75.4, CID:5 = - 60.9 kJ/mol) than ceftazidime (- 34.5 kJ/mol). The drug-like properties of the selected compounds were relatively similar to those of ceftazidime, and the toxicity predictions categorized these compounds into less toxic classes. Structural similarity and functional group analyses suggested that the presence of more H-acceptor atoms, electronegative atoms, acidic oxygen groups, and nitrogen atoms in amide or aromatic groups were common among the compounds with the lowest binding affinities. In conclusion, this in silico work predicts for the first time the potential of using five R. stricta nonalkaloid compounds as a treatment strategy to control SARS-CoV-2 viral entry.

Apocynaceae , COVID-19 , Plants, Medicinal , COVID-19/drug therapy , Ceftazidime , Humans , Molecular Docking Simulation , SARS-CoV-2
Molecules ; 27(9)2022 May 04.
Article in English | MEDLINE | ID: covidwho-1820345


(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

COVID-19 , Euphorbia , COVID-19/drug therapy , Euphorbia/metabolism , Flavonoids/pharmacology , Glycoproteins , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306121


The recent emerging SARS-CoV-2 pandemic which was identified as COVID-19 disease has become a global health concern. It resulted in a major pneumonia outbreak worldwide. Currently, there are no approved drugs and several attempts have been made to use computational program approaches in drug repurposing for COVID-19 treatment. The SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) is vital for binding to the hACE2 receptor, which initiates entry into human cells, and thus is a key target for antiviral compound development. Many herbal natural products have been proved to exert virucidal activity against the vast majority of pathogenic viruses. Rhazya stricta , a folkloric medicinal desert plant of Saudi Arabia was shown to exhibit bactericidal activity against a verity of pathogens including Methicillin-resistant Staphylococcus aureus (MRSA) and some other Multidrug-Resistant Organisms (MDR’s). This study aims to test for antiviral activity of the folkloric medicinal desert plant Rhazya stricta against coronavirus SARS-CoV-2. We identified three non-alkaloid herbal natural compounds Lig230, Lig434, and Lig68 from Rhazya Stricta that bind and interact significantly with RBD (PDB: I.D. 6M0J) by using virtual screening and computer aiding program Autodock vina. Based on the results of docking scores, molecular docking simulations, RMSD, RMSF, and radius of gyration (Rg), the virtually screened antiviral compounds showed good binding interactions and high stability. Lig230 revealed the highest average of interaction energy during MD simulation (− 417.284 kJ/mol) followed by Lig434 (− 366.186 kJ/mol) and the lowest interaction energy was by Lig68 (− 352.5872 kJ/mol). To evaluate the oral bioavailability, a drug-likeness profile was performed by SwissADME and the results revealed that these compounds expected to confront permeability and solubility difficulties if they were introduced orally. In conclusion, the suggested three compounds can serve as potential anti- SARS-CoV-2 and should be furtherly tested in vitro and in vivo .