Comprehensive In Silico Screening of the Antiviral Potentialities of a New Humulene Glucoside from Asteriscus hierochunticus against SARS-CoV-2

Imieje, Vincent; Zaki, Ahmed A.; Metwaly, Ahmed M.; Mostafa, Ahmad E.; Falodun, Abiodun

doi:10.1155/2021/5541876

Cited by 13 publications

(16 citation statements)

References 49 publications

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“…Scientists isolated the secondary metabolites produced by these natural sources and labeled them as the key element in bioactivity. These candidates belonged to various classes as isochromenes [39], α-pyrones [40], diterpenes [41,42], sesquiterpenes [43,44], steroids [45], flavonoids [46,47], alkaloids [48], and saponins [49,50]. SARS-CoV-2 is an enveloped positive-sensed RNA virus.…”

Section: Introductionmentioning

confidence: 99%

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

et al. 2021

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In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.

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Section: Introductionmentioning

confidence: 99%

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

et al. 2021

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“…Fraction 5 was further purified utilizing Sephadex LH-20 to afford the crystalline substance (1) a yellow color with a m.p. more than 350 • C. Based on the spectral data of UV, 1 H, and 13 C NMR, with two-dimensional experiments, HSQC, Dept, COSY, and HMBC (Table 1), compound 1 was identified to be the new compound 5,2 ,4 -trihydroxy-6,7,5 -trimethoxyflavone, Jusanin (Figure 1).…”

Section: Isolation Of Jusaninmentioning

confidence: 99%

“…more than 350 °C. Based on the spectral data of UV, 1 H, and 13 C NMR, with two-dimensional experiments, HSQC, Dept, COSY, and HMBC (Table 1), compound 1 was identified to be the new compound 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone, Jusanin (Figure 1). The molecular formula C18H16O8 was decided by the HR-ESI-MS experiment, (+ve mode), that displayed a pseudo molecular ion peak [M + H] + at m/z 361.0934 (calcd.…”

Section: Isolation Of Jusaninmentioning

confidence: 99%

“…NMR spectra were carried out on a commercial instrument (Bruker Avance 300 a 600 MHz), chemical shifts () are presented in parts per million (ppm) and re-calculat with respect to tetramethylsilane (TMS) ( 1 H) or carbon signals of deuterium solvents ( 13 C Spin-spin coupling constants (J) are given in hertz (Hz). The refinement of 13 C NMR sp tra signals was carried out using Dept, HSQC, HMBC NMR spectra. Mass spectra we recorded on an HP5989A instrument (CI and EI, ionization energy 70 eV) with Apollo 3 data, and on a Kratos MS50TC instrument for accurate calculations (reaching by elect shock (ESI), common solvent mixture: CH2Cl2 -MeOH  NH4OAc) with MASSLYNX syste data.…”

Section: General Experimental Sectionmentioning

confidence: 99%

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Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease

et al. 2022

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A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein’s active site with a binding energy of −19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and β-sitosterol (4).

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“…These approaches have been practiced fruitfully and frequently in several scientific studies to find a treatment against COVID-19 with the advantage of taking less effort, time, and cost [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies

et al. 2021

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Papain-like protease is an essential enzyme in the proteolytic processing required for the replication of SARS-CoV-2. Accordingly, such an enzyme is an important target for the development of anti-SARS-CoV-2 agents which may reduce the mortality associated with outbreaks of SARS-CoV-2. A set of 69 semi-synthesized molecules that exhibited the structural features of SARS-CoV-2 papain-like protease inhibitors (PLPI) were docked against the coronavirus papain-like protease (PLpro) enzyme (PDB ID: (4OW0). Docking studies showed that derivatives 34 and 58 were better than the co-crystallized ligand while derivatives 17, 28, 31, 40, 41, 43, 47, 54, and 65 exhibited good binding modes and binding free energies. The pharmacokinetic profiling study was conducted according to the four principles of the Lipinski rules and excluded derivative 31. Furthermore, ADMET and toxicity studies showed that derivatives 28, 34, and 47 have the potential to be drugs and have been demonstrated as safe when assessed via seven toxicity models. Finally, comparing the molecular orbital energies and the molecular electrostatic potential maps of 28, 34, and 47 against the co-crystallized ligand in a DFT study indicated that 28 is the most promising candidate to interact with the target receptor (PLpro).

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Comprehensive In Silico Screening of the Antiviral Potentialities of a New Humulene Glucoside from Asteriscus hierochunticus against SARS-CoV-2

Cited by 13 publications

References 49 publications

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease

In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies

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