Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective

Duru, Chidi Edbert; Umar, Haruna Isiyaku; Duru, Ijeoma Akunna; Enenebeaku, Uchechi E.; Ngozi-Olehi, Lynda Chioma; Enyoh, Christian Ebere

doi:10.5620/eaht.2021010

Cited by 11 publications

(12 citation statements)

References 25 publications

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“…Após a triagem de títulos e resumos, 25 estudos foram analisados quanto aos critérios de inclusão e 16 foram excluídos. Os artigos foram excluídos por não apresentarem o desenho de estudo previamente definido Campos, Fulco, et al, 2020;Chitsike & Duerksen-Hughes, 2021;Cicka & Sukhatme, 2021;Duru et al, 2021;García-Álvarez & García-Vigil, 2020;Kelleni, 2020Kelleni, , 2021Lisi et al, 2020;Martins-Filho et al, 2020;Mostafa et al, 2020;Olagunju et al, 2021;Paumgartten et al, 2020;Rajoli et al, 2020;Ribeiro et al, 2021).…”

Section: Resultsunclassified

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Santos

Neto²,

Rocha³

et al. 2022

RSD

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Objetivos: Revisar sistematicamente a literatura científica acerca das evidências sobre o uso de ivermectina e nitazoxanida como tratamento e profilaxia para a COVID-19. Metodologia: Esta revisão sistemática foi desenvolvida de acordo com o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As bases bibliográficas PubMed, Lilacs e SciELO foram pesquisadas em 14 de outubro de 2021 para identificar estudos que avaliaram o uso de ivermectina e nitazoxanida para tratamento ou profilaxia de casos confirmados ou suspeitos de COVID-19. Resultados: Foram recuperados 105 artigos, dos quais 9 foram incluídos para a revisão final, quatro ensaios clínicos randomizados, um ensaio clínico não randomizado, uma coorte retrospectiva, um estudo transversal, uma série de casos e um relato de caso. A maioria dos estudos eram do Brasil, Egito e México, avaliaram a nitazoxanida e abordaram o tratamento da doença. Conclusões: Não existem evidências científicas suficientemente robustas para apoiar o tratamento e/ou a profilaxia com a ivermectina e nitazoxanida para a COVID-19. Apesar dos resultados encontrados não apontarem um risco aumentado de eventos adversos aos medicamentos analisados, não se deve presumir que seu uso é isento de riscos e estes devem ser usados de maneira racional.

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Section: Resultsunclassified

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Santos

Neto²,

Rocha³

et al. 2022

RSD

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“…The multiple ligand docking of the main compounds in todomatsu oil on the Der f 2 was done with AutoDock Vina in PyRx software version 0.8 (San Diego, CA, USA) [ 40 , 52 , 53 ]. In brief, the compounds were docked blindly at the Der f 2 cavities to allow the ligands unrestricted access to engaging with sites with the lowest energy.…”

Section: Methodsmentioning

confidence: 99%

Novel Approaches for Inhibiting the Indoor Allergen Der f 2 Excreted from House Dust Mites by Todomatsu Oil Produced from Woodland Residues

Lin

Enyoh

Wang

et al. 2022

IJERPH

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House dust mite (HDM) is a globally ubiquitous domestic cause of allergic diseases. There is a pressing demand to discover efficient, harmless, and eco-friendly natural extracts to inhibit HDM allergens that are more likely to trigger allergies and challenging to be prevented entirely. This study, therefore, is aimed at assessing the inhibition of the allergenicity of major HDM allergen Der f 2 by todomatsu oil extracted from residues of Abies Sachalinensis. The inhibition was investigated experimentally (using enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)) and in silico using molecular docking. The results showed that todomatsu oil inhibits the allergenicity of Der f 2 by reducing its amount instead of the IgG binding capacity of a single protein. Moreover, the compounds in todomatsu oil bind to Der f 2 via alkyl hydrophobic interactions. Notably, most compounds interact with the hydrophobic amino acids of Der f 2, and seven substances interact with CYS27. Contrarily, the principal compounds fail to attach to the amino acids forming the IgG epitope in Der f 2. Interestingly, chemical components with the lowest relative percentages in todomatsu oil show high-affinity values on Der f 2, especially β-maaliene (−8.0 kcal/mol). In conclusion, todomatsu oil has been proven in vitro as a potential effective public health strategy to inhibit the allergenicity of Der f 2.

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“…When compared to some present drugs, the binding affinity value is not far from the mentioned ligands in Table 2. From Duru et al (2021), there are various drugs that are assessed for binding affinity with ACE2 and spike glycoprotein [32]. The drugs that have potential highest binding affinity are lopinavir, ritonavir, nafamostat, ivermectin, and camostat.…”

Section: Molecular Docking Of Ligands To Human Ace2 Protein and Sars-...mentioning

confidence: 99%

“…Additionally binding affinity of drugs with spike glycoprotein include ivermectin (-9.0 kcal/mol), nafamostat (-7.8 kcal/mol), and camostat (-7.4 kcal/mol), lopinavir (-7.3 kcal/mol), and ritonavir (-6.9 kcal/mol). According to the study, nafamostat has good potential as an inhibitor compound due to the dual bridging characteristic with both ACE2 and spike protein [32]. These drugs binding affinity, when compared against Spike-ACE2 complex binding affinity, is still lower.…”

Section: Molecular Docking Of Ligands To Human Ace2 Protein and Sars-...mentioning

confidence: 99%

“…When compared to the ligands, friedelin is the highest one that has comparable value with the other drugs; therefore, flavonoids might be able to be used as COVID-19 treatment. However, it is important to note that there may be differences in the parameters or protein structures used in the molecular docking study of Duru et al (2021) [32] and this study. Therefore, a study to compare the binding affinity and interactions between the compounds (flavonoids and the mentioned drugs) and the human ACE2 and SARS-CoV-2 Spike protein can be done.…”

Section: Molecular Docking Of Ligands To Human Ace2 Protein and Sars-...mentioning

confidence: 99%

See 1 more Smart Citation

Identification of Flavonoids of Kalanchoe Pinnata as Candidate Drugs for COVID-19 Gamma-Variant Treatment

Aurora

Tarigan

Suryanto

et al. 2022

Mal. J. Fund. Appl. Sci.

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Treatment of COVID-19 that is based on plants could be a more cost-effective therapy against the disease. Flavonoids, a group of compounds that have been observed to have various effects, including antiviral activity, were chosen as the candidate molecule for treatment of COVID-19. Kalanchoe Pinnata is one of the plants containing flavonoids that has been demonstrated to have antiviral activity. The structure of ACE2 and various flavonoids were retrieved and cleaned from unnecessary residues. The ACE2 structure was subjected to molecular docking in order to analyze the binding affinity. Following that, the ADME properties of each flavonoid were analyzed accordingly. The QSAR analysis was also performed for each type of flavonoid. Lastly, molecular dynamics simulation was conducted. All of the tested compounds were able to bind to human ACE2 and SARS-CoV-2 Spike protein, but were unable to compete with them as the binding affinity of the compounds to the protein were lower compared to ACE2-Spike interaction. The ADME and toxicity analysis showed that most of the ligands were able to be absorbed by the GI tract, but have low bioavailability. The compounds also cause no major toxicity effects and were able to be sufficiently distributed to the body. Molecular dynamics analysis also revealed that among the compounds, quercetin and rutin were able to interact with ACE2 and Spike protein stably. The QSAR analysis showed that friedelin, kaempferol, quercetin, and rutin are mostly non-toxic, but the high Cramer values indicate that there are no initial safety impressions for these molecules and could cause toxicity. In conclusion, quercetin and rutin have potential to be a candidate for COVID-19 drug development based on the in-silico predictions results obtained. Friedelin and Narcissin whose affinity to the proteins were relatively stronger but had unstable interactions from molecular dynamics simulation results, may also be a potential COVID-19 treatment with further investigation. However, further research is required to assess the effectiveness and also specially to measure the toxicity of the compounds.

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Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective

Cited by 11 publications

References 25 publications

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Novel Approaches for Inhibiting the Indoor Allergen Der f 2 Excreted from House Dust Mites by Todomatsu Oil Produced from Woodland Residues

Identification of Flavonoids of Kalanchoe Pinnata as Candidate Drugs for COVID-19 Gamma-Variant Treatment

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