Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Abouelela, Mohamed E.; Assaf, Hamdy K.; Abdelhamid, Reda A.; Elkhyat, Ehab S; Sayed, Ahmed M.; Oszako, Tomasz; Belbahri, Lassaâd; Zowalaty, Ahmed E. El; Abdelkader, Mohamed Salaheldin A.

doi:10.3390/molecules26061767

Cited by 36 publications

(27 citation statements)

References 173 publications

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“…In silico studies showed that anthraquinones (aloe emodin, aloinoside A, aloeresin D, Isoaloeresin A, etc. ), phenolic compounds (pyrocatechol, p-Hydroxyacetophenone), and fatty acid derivatives (10-Hydroxyoctadecanoic acid, 10- Oxooctadecanoic acid) are potential SARS-CoV-2 main protease inhibitors [107]. Similar to A. vera, A. ferox is well endowed with antiinflammatory compounds [108,109].…”

Section: Aloe Feroxmentioning

confidence: 99%

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox

et al. 2021

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Background Aloe vera and Aloe ferox have over the years been among the most sought-after Aloe species in the treatment of ailments worldwide. This review provides categorized literature on the phytochemical and scientifically proven toxicological profiles of A. vera and A. ferox to facilitate their exploitation in therapy. Main body of the abstract Original full-text research articles were searched in PubMed, ScienceDirect, Research gate, Google Scholar, and Wiley Online Library using specific phrases. Phenolic acids, flavonoids, tannins, and anthraquinones were the main phytochemical classes present in all the two Aloe species. Most of the phytochemical investigations and toxicity studies have been done on the leaves. Aloe vera and Aloe ferox contain unique phytoconstituents including anthraquinones, flavonoids, tannins, sterols, alkaloids, and volatile oils. Aloe vera hydroalcoholic leaf extract showed a toxic effect on Kabir chicks at the highest doses. The methanolic, aqueous, and supercritical carbon dioxide extracts of A. vera leaf gel were associated with no toxic effects. The aqueous leaf extract of A. ferox is well tolerated for short-term management of ailments but long-term administration may be associated with organ toxicity. Long-term administration of the preparations from A. vera leaves and roots was associated with toxic effects. Short conclusion This review provides beneficial information about the phytochemistry and toxicity of A. vera and A. ferox and their potential in the treatment of COVID-19 which up to date has no definite cure. Clinical trials need to be carried out to clearly understand the toxic effects of these species.

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Section: Aloe Feroxmentioning

confidence: 99%

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox

et al. 2021

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“…Recently two different randomized controlled trials of A. indica extract/capsule on COVID-19 positive patients established the significant anti-SARS-CoV-2 potential in A. indica plant (Khan et al, 2020;Nesari et al, 2021). Similarly, few studies reported the Aloe vera phytochemicals as SARS-CoV-2 M pro and RdRp binding potential (Mpiana et al, 2020;Abouelela et al, 2021;Balkrishna et al, 2021). These studies either considered fewer compounds or concerned only the Aloe vera-specific phytochemicals for the study.…”

Section: Introductionmentioning

confidence: 99%

Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach

Kushwaha

Singh

Bansal

et al. 2021

Front. Cell. Infect. Microbiol.

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The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in Mpro-unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the Mpro-ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 Mpro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential.

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“…In the same cluster, compound 14 or Aloesinol_7-Me_ether The compounds identified using DEREPLICATOR+, in the GNPS website, are present in a recently published review [26]. Using the chemical structures isolated from the Genus Aloes and the in silico study reveals that several compounds are potential actives against the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2).…”

Section: Identification Of Specialized Metabolites Using Lc-ms/ms Molecular Networking Based-approachmentioning

confidence: 99%

Aloe djiboutiensis: Antioxidant Activity, Molecular Networking-Based Approach and In Vivo Toxicity of This Endemic Species in Djibouti

et al. 2021

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For the first time, the study of the antioxidant activity, the characterization of the phytoconstituants, and the evaluation of in vitro and in vivo toxicity of A. djiboutiensis leave and latex are performed. The antioxidant activity of both latex (ADL) and the methanolic extract of leaves (ADM) is determined using 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging radical methods and ferric reducing/antioxidant power (FRAP) assay. The phytochemical study of latex is done using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and a molecular networking-based approach. The evaluation of in vivo toxicity is performed on mice by oral gavage with a suspension of ADL. Our results show that weak antioxidant activity of ADL and ADM in opposition to their high polyphenol, 83.01 mg and 46.4 mg expressed in gallic acid equivalent (GAE)/g of dry weight (DW), respectively, and flavonoid contents 13.12 mg and 4.25 mg expressed in quercetin equivalent (QE)/g dry weight (DW), respectively. Using the Global Natural Products Social Molecular Networking (GNPS) website, nine (9) anthraquinones derivatives, ten (10) chromones derivatives, two (2) flavonols/ chromones isomers are annotated in the molecular network. The treated mice do not display abnormalities in their general physical appearance and biochemistry parameters, compared to the controls. Only glucose and calcium levels are slightly higher in male treated mice compared to the vehicles.

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Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Cited by 36 publications

References 173 publications

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox

Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach

Aloe djiboutiensis: Antioxidant Activity, Molecular Networking-Based Approach and In Vivo Toxicity of This Endemic Species in Djibouti

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