Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and In vitro assays DOI Creative Commons
Ahmed M. Metwaly,

Esmail M. El-Fakharany,

Aisha A. Alsfouk

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0312866 - e0312866

Опубликована: Дек. 3, 2024

To find an effective inhibitor for SARS-CoV-2, Quercetin’s chemical structure was compared to nine ligands associated with key SARS-CoV-2 proteins. It found that Quercetin closely resembles Remdesivir, the co-crystallized ligand of RNA-dependent RNA polymerase (RdRp). This similarity confirmed through flexible alignment experiments and molecular docking studies, which showed both Remdesivir bind similarly active site RdRp. Molecular dynamics (MD) simulations over a 200 ns trajectory, analyzing various factors like RMSD, RG, RMSF, SASA, hydrogen bonding were conducted. These gave detailed insights into binding interactions RdRp Remdesivir. Further analyses, including MM-GBSA, Protein-Ligand Interaction Fingerprints (ProLIF) Profile PLIP stability binding. Principal component analysis trajectories (PCAT) provided coordinated movements within systems studied. In vitro assays is highly in inhibiting RdRp, IC 50 122.1 ±5.46 nM, better than Remdesivir’s 21.62 ±2.81 μM. Moreover, greater efficacy against , 1.149 μg/ml 9.54 μg/ml. The selectivity index (SI) values highlighted safety margin (SI: 791) 6). conclusion, our comprehensive study suggests promising candidate further research as providing valuable developing anti-COVID-19 treatment.

Язык: Английский

Pharmacophore modeling and QSAR analysis of anti-HBV flavonols DOI Creative Commons

Basireh Baei,

Parnia Askari,

Fatemeh Sana Askari

и другие.

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0316765 - e0316765

Опубликована: Янв. 13, 2025

Due to its global burden, Targeting Hepatitis B virus (HBV) infection in humans is crucial. Herbal medicine has long been significant, with flavonoids demonstrating promising results. Hence, the present study aimed establish a way of identifying anti-HBV activities. Flavonoid structures activities were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening performed PharmIt server. QSAR equation developed and validated independent sets compounds. The applicability domain (AD) defined Euclidean distance calculations for validation. best model, consisting 57 features, generated. High-throughput screening (HTS) resulted 509 unique hits. model's accuracy further set FDA-approved chemicals, sensitivity 71% specificity 100%. Additionally, two predictors, x4a qed, exhibited predictive solid performance an adjusted-R2 value 0.85 0.90 Q2. PCA showed essential patterns relationships within dataset, first components explaining nearly 98% total variance. Current HBV therapies tend fail provide complete cure, emphasizing need new therapies. This study's importance highlight flavonols as potential medicines, presenting supplementary option existing therapy. separate chemical sets, guaranteeing reproducibility usefulness other by utilizing characteristics X4A qed. These results possibilities discovering future drugs integrating modeling experimental research.

Язык: Английский

Процитировано

2
The dynamic States of Hepatitis B virus Capsid Monomers under the Impact of Different Class of Capsid-Assembly Modulators DOI Creative Commons
Fatemeh Sana Askari, Alireza Mohebbi

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

Abstract Hepatitis B virus (HBV) remains a global health challenge. Capsid assembly modulators (CAMs) represent promising class of antiviral agents that disrupt HBV core protein (HBc) function. Understanding the structural and dynamic impact CAMs on HBc is crucial for development next-generation therapies. This study employed molecular dynamics (MD) simulations to evaluate conformational behavior monomers in unbound ligand-bound states. Different classes CAMs—Heteroaryldihydropyrimidine (HAP), Sulfamoylbenzamide (SBA), Ciclopirox—were analyzed assess their stability, flexibility, interaction energy. RMSD analysis revealed HAP binding stabilized HBc, reducing backbone fluctuations, whereas SBA PPA increased flexibility. RMSF calculations demonstrated CAM interactions influenced loop terminal region dynamics. PCA suggested ligand-specific alterations HBc’s essential motions, with inducing highest variance. Salt bridge indicated Ciclopirox formed strongest electrostatic interactions, stabilizing its binding. DSSP secondary structure showed disrupted α-helical content, exhibiting most pronounced rearrangements. provides novel insights into CAM-induced changes HBc. While stabilizes protein, increase potentially leading misassembled or destabilized capsids. These findings contribute rational design CAM-based therapies highlight key determinants future drug optimization.

Язык: Английский

Процитировано

0
Potential Benefits of In Silico Methods: A Promising Alternative in Natural Compound’s Drug Discovery and Repurposing for HBV Therapy DOI Creative Commons
Samuel Chima Ugbaja, Aganze Gloire-Aimé Mushebenge, Hezekiel M. Kumalo

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 419 - 419

Опубликована: Март 16, 2025

Hepatitis B virus (HBV) is an important global public health issue. The World Health Organization (WHO) 2024 Global Report estimated that the prevalence of people living with HBV infection 254 million, incidence 1.2 million new infections yearly. Previous studies have shown natural compounds antiviral inhibition potentials. In silico methods such as molecular docking, virtual screening, pharmacophore modeling, quantitative structure–activity relationship (QSAR), and dynamic simulations been successfully applied in identifying bioactive strong binding energies treatment targets. COVID-19 pandemic necessitated importance repurposing already approved drugs using methods. This study aimed at unveiling benefits techniques a potential alternative compounds’ drug discovery for therapy. Relevant articles from PubMed, Google Scholar, Web Science were retrieved analyzed. Furthermore, this comprehensively reviewed literature containing identified essential proteins. Notably, hesperidin, quercetin, kaempferol, myricetin, flavonoids hepatitis surface antigen (HBsAg). investigation reveals offer understanding mechanisms action, reveal previously overlooked viral targets (including PreS1 Domain HBsAg cccDNA (Covalently Closed Circular DNA) regulators, facilitate creation specific inhibitors. integration silico, vitro, vivo insights further highlight Moreover, combination compounds, approach, improves chances personalized precision medicine treatment. Therefore, we recommend strategies combine vivo, approaches to effective drugs.

Язык: Английский

Процитировано

0
Facile Synthesis and Applications of Flavonoid-Heterocyclic Derivatives DOI
Saba Farooq, Zainab Ngaini

Current Topics in Medicinal Chemistry, Год журнала: 2024, Номер 25(1), С. 47 - 62

Опубликована: Июнь 19, 2024

Flavonoids belong to the polyphenol group that naturally exists in fruits, vegetables, tea, and grains. Flavonoids, as secondary metabolites, show indispensable contributions biological processes responses of plants numerous environmental factors. The bioactivity flavonoids depends on C6-C3-C6 ring substitution patterns exhibit bioactive antioxidant, antimicrobial, antifungal, antitumor, anti-inflammatory properties. synthesis has been reported by various methodologies. Therefore, present review systematically summarizes recent heterocyclic flavonoid derivatives via facile synthetic approaches since research is useful for therapeutic biotechnology fields.

Язык: Английский

Процитировано

2
Ligand-based pharmacophore modeling, virtual screening, and 2D quantitative structure-activity relationship performance on anti-Hepatitis B virus flavonols DOI Open Access
Alireza Mohebbi, Fatemeh Sana Askari,

Parnia Askari

и другие.

Опубликована: Март 28, 2024

Background: Targeting Hepatitis B virus (HBV) infection in human is crucial due to its adverse. Herbal medicine has long been significant this regard, with flavonoids demonstrating promising results. Hence, establishing a way of identifying anti-HBV activities the aim present study. Methods: Flavonoid structures were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening performed PharmIt server. QSAR equation developed and validated independent sets compounds. Applicability domain (AD) defined Euclidean distance calculations for validation. Results: The best model, consisting 57 features generated. HTS resulted 509 unique hits. model's sensitivity specificity 71% 100%, respectively. two predictors, x4a qed, exhibited strong predictive performance an adjusted-R² value 0.85 0.90 Q2. Conclusion: separate chemical sets, guaranteeing reproducibility usefulness other flavonols by utilizing characteristics X4A qed. These results provide new possibilities discovering future drugs integrating modeling experimental research.

Язык: Английский

Процитировано

0
Mechanistic insights of the anti-ageing dietary plant secondary metabolites vis-à-vis the modern hallmarks of ageing: implications for developing novel anti-ageing foods DOI Creative Commons
Rohit Sharma, Anamika Sharma

Translational Medicine of Aging, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0
Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and In vitro assays DOI Creative Commons
Ahmed M. Metwaly,

Esmail M. El-Fakharany,

Aisha A. Alsfouk

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0312866 - e0312866

Опубликована: Дек. 3, 2024

To find an effective inhibitor for SARS-CoV-2, Quercetin’s chemical structure was compared to nine ligands associated with key SARS-CoV-2 proteins. It found that Quercetin closely resembles Remdesivir, the co-crystallized ligand of RNA-dependent RNA polymerase (RdRp). This similarity confirmed through flexible alignment experiments and molecular docking studies, which showed both Remdesivir bind similarly active site RdRp. Molecular dynamics (MD) simulations over a 200 ns trajectory, analyzing various factors like RMSD, RG, RMSF, SASA, hydrogen bonding were conducted. These gave detailed insights into binding interactions RdRp Remdesivir. Further analyses, including MM-GBSA, Protein-Ligand Interaction Fingerprints (ProLIF) Profile PLIP stability binding. Principal component analysis trajectories (PCAT) provided coordinated movements within systems studied. In vitro assays is highly in inhibiting RdRp, IC 50 122.1 ±5.46 nM, better than Remdesivir’s 21.62 ±2.81 μM. Moreover, greater efficacy against , 1.149 μg/ml 9.54 μg/ml. The selectivity index (SI) values highlighted safety margin (SI: 791) 6). conclusion, our comprehensive study suggests promising candidate further research as providing valuable developing anti-COVID-19 treatment.

Язык: Английский

Процитировано

0