Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

Alhadrami, Hani A.; Burgio, Gaia; Thissera, Bathini; Orfali, Raha; Jiffri, Suzan E.; Yaseen, Mohammed; Sayed, Ahmed M.; Rateb, Mostafa E.

doi:10.3390/md20030163

Cited by 27 publications

(34 citation statements)

References 43 publications

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“…As previously described, binding free energy estimation (∆G binding) and molecular dynamic simulations were performed [ 52 , 53 ]. The Supplementary Materials file has a detailed description of these procedures.…”

Section: Methodsmentioning

confidence: 99%

¹H-NMR Metabolic Profiling, Antioxidant Activity, and Docking Study of Common Medicinal Plant-Derived Honey

et al. 2022

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The purpose of this investigation was to determine ¹H-NMR profiling and antioxidant activity of the most common types of honey, namely, citrus honey (HC1) (Morcott tangerine L. and Jaffa orange L.), marjoram honey (HM1) (Origanum majorana L.), and clover honey (HT1) (Trifolium alexandrinum L.), compared to their secondary metabolites (HC2, HM2, HT2, respectively). By using a ¹H-NMR-based metabolomic technique, PCA, and PLS-DA multivariate analysis, we found that HC2, HM2, HC1, and HM1 were clustered together. However, HT1 and HT2 were quite far from these and each other. This indicated that HC1, HM1, HC2, and HM2 have similar chemical compositions, while HT1 and HT2 were unique in their chemical profiles. Antioxidation potentials were determined colorimetrically for scavenging activities against DPPH, ABTS, ORAC, 5-LOX, and metal chelating activity in all honey extract samples and their secondary metabolites. Our results revealed that HC2 and HM2 possessed more antioxidant activities than HT2 in vitro. HC2 demonstrated the highest antioxidant effect in all assays, followed by HM2 (DPPH assay: IC50 2.91, 10.7 μg/mL; ABTS assay: 431.2, 210.24 at 50 ug/mL Trolox equivalent; ORAC assay: 259.5, 234.8 at 50 ug/mL Trolox equivalent; 5-LOX screening assay/IC50: 2.293, 6.136 ug/mL; and metal chelating activity at 50 ug/mL: 73.34526%, 63.75881% inhibition). We suggest that the presence of some secondary metabolites in HC and HM, such as hesperetin, linalool, and caffeic acid, increased the antioxidant activity in citrus and marjoram compared to clover honey.

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Section: Methodsmentioning

confidence: 99%

¹H-NMR Metabolic Profiling, Antioxidant Activity, and Docking Study of Common Medicinal Plant-Derived Honey

et al. 2022

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“…The in silico analysis revealed that the molecule aurasperone A targets M pro in SARS-CoV-2 [152]. Furthermore, neoechinulin A isolated from Aspergillus fumigatus MR2012 from the Red Sea exhibited an IC 50 value of 0.47 µM against SARS-CoV-2, with a similar target to M pro [153]. NeoB, an anti-HBV alkaloid isolated from A. amstelodami, also demonstrated anti-SARS-CoV-2 activity, inhibiting liver X receptors [20].…”

Section: Anti-sars-cov-2mentioning

confidence: 99%

“…M pro plays an essential role in the replication and transcription of SARS-CoV-2. There are a number of microbe-produced natural products with the ability to inhibit M pro , including aurasperone A [152]; neoechinulin A [153]; as well as aspulvinone D, M, and R [154].…”

Section: Possible Targetmentioning

confidence: 99%

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review

et al. 2022

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The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease.

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“…Meanwhile, quercetin and caffeic acid were reported as 3CL protease inhibitors [ 13 ]. To accelerate the discovery of antiviral hits against SARS-CoV-2, molecular docking for thousands of known phyto-constituents was performed on the main protease by utilizing computer-aided programs [ 14 , 15 , 16 , 17 ]. The compounds with high activity in virtual screening encourage researchers to test them in vitro on SARS-CoV-2 M PRO .…”

Section: Introductionmentioning

confidence: 99%

“…The compounds with high activity in virtual screening encourage researchers to test them in vitro on SARS-CoV-2 M PRO . These studies afforded many active compounds against the main protease, such as neoechinulin A from Red-Sea-derived Aspergillus fumigatus MR2012 [ 16 ], naringenin [ 17 ], and cnicin from Carduus benedictus [ 18 ]. Moreover, thirty-eight African medicinal plants traditionally used as an antiviral and immunomodulator and for treating COVID-19 symptoms were reviewed previously to open the door for drug discovery from medicinal plants [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

Abdallah

El-Halawany

Darwish

et al. 2022

Plants

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Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand–target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

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Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

Cited by 27 publications

References 43 publications

¹H-NMR Metabolic Profiling, Antioxidant Activity, and Docking Study of Common Medicinal Plant-Derived Honey

¹H-NMR Metabolic Profiling, Antioxidant Activity, and Docking Study of Common Medicinal Plant-Derived Honey

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

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