Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 DOI Creative Commons
Ahmed H. Bakheit, Quaiser Saquib, Sarfaraz Ahmed

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(11), P. 2175 - 2175

Published: Oct. 30, 2023

COVID-19, a disease caused by SARS-CoV-2, has huge loss of human life, and the number deaths is still continuing. Despite lack repurposed drugs vaccines, search for potential small molecules to inhibit SARS-CoV-2 in demand. Hence, we relied on drug-like characters ten phytochemicals (compounds 1–10) that were previously isolated purified our research team from Saudi medicinal plants. We computationally evaluated inhibition RNA-dependent RNA polymerase (RdRp) compounds 1–10. Non-covalent (reversible) docking 1–10 with RdRp led formation hydrogen bond template primer nucleotides (A U) key amino acid residues (ASP623, LYS545, ARG555, ASN691, SER682, ARG553) its active pocket. Covalent (irreversible) revealed 7, 8, 9 exhibited their irreversible nature binding CYS813, crucial palm domain RdRP. Molecular dynamic (MD) simulation analysis RMSD, RMSF, Rg parameters affirmed RdRP complexes stable showed less deviation. Our data provide novel information demonstrated non-nucleoside interaction capabilities shed new scaffolds as antivirals against SARS-CoV-2.

Language: Английский

Synthesis of Isolated DNA Aptamer and Its Application of AC-Electrothermal Flow-Based Rapid Biosensor for the Detection of Dengue Virus in a Spiked Sample DOI

Hanbin Park,

Ho Seok Lee, Myoungro Lee

et al.

Bioconjugate Chemistry, Journal Year: 2023, Volume and Issue: 34(8), P. 1486 - 1497

Published: Aug. 1, 2023

Dengue fever is an infectious disease caused by the dengue virus (DENV) and transmitted mosquitoes in tropical subtropical regions. The early detection method at a low cost essential. To address this, we synthesized isolated DENV aptamer for fabricating rapid electrochemical biosensor on Au interdigitated microgap electrode (AuIMGE). aptamers were generated using SELEX (systemic evolution of ligands exponential enrichment) binding to surface envelope proteins. reduce manufacturing cost, unnecessary nucleotide sequences excluded from isolation process aptamer. time, alternating current electrothermal flow (ACEF) technique was applied fabricated biosensor, which can shorten time 10 min. performance evaluated cyclic voltammetry (CV) impedance spectroscopy (EIS). In diluted protein solution, linear range concentrations 1 pM μM LOD 76.7 fM. Moreover, proposed detected spiked sample 10–6 106 TCID50/mL, while proven with 1.74 × 10–7 TCID50/mL along high selectivity.

Language: Английский

Citations

9
Recent advancements in the discovery of small-molecule non-nucleoside inhibitors targeting SARS-CoV-2 RdRp DOI Open Access

Bangdi Zhou,

D. Chen,

Tingyan Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116180 - 116180

Published: Jan. 23, 2024

The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 plays a pivotal role in the life cycle novel coronavirus and stands as significant promising target for anti-SARS-CoV-2 drugs. Non-nucleoside inhibitors (NNIs), category compounds directed against RdRp, exhibit unique highly effective mechanism, effectively overcoming various factors contributing to drug resistance nucleoside (NIs). This review investigates NNIs, including both natural synthetic inhibitors, that closely interacting with RdRp valid evidences from vitro silico studies.

Language: Английский

Citations

3
Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics DOI Creative Commons
L Tóth, Kateřina Krejčová, Milan Dejmek

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 20, P. 1029 - 1036

Published: May 6, 2024

The RNA-dependent RNA polymerase (RdRp) represents a prominent target in the discovery and development of new antivirotics against viruses, inhibiting replication process. One most targeted viruses last years is, without doubt, SARS-CoV-2, cause recent COVID-19 pandemic. HeE1-2Tyr, known inhibitor flaviviral RdRp, has been discovered to also have antiviral potency this coronavirus. In study, we report three distinct modifications HeE1-2Tyr: conversion core from benzothiazole benzoxazole moiety two different scaffold simplifications, respectively. We provide novel synthetic approach and, addition, evaluate final molecules an vitro assay for biological activity.

Language: Английский

Citations

3
The fed-batch production of mannosylerythritol lipids by Ustilago maydis DSM 4500 from hydrophilic carbon sources DOI Creative Commons
André D. Valkenburg, George M. Teke, Robert W. M. Pott

et al.

Bioprocess and Biosystems Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 21, 2024

Language: Английский

Citations

3
Recent advances in the piperazine based antiviral agents: A remarkable heterocycle for antiviral research DOI Creative Commons
Kamran Walayat, Noor ul Amin Mohsin, Sana Aslam

et al.

Arabian Journal of Chemistry, Journal Year: 2023, Volume and Issue: 16(12), P. 105292 - 105292

Published: Sept. 25, 2023

A growing interest in pharmacology has made heterocyclic chemistry as one of the emerging branches organic chemistry. Piperazine is an excellent heterocycle that possesses a large span pharmaceutical applications. derived compounds have shown multiple therapeutic activities such antioxidant, antibacterial, analgesic, anticancer, antihypertensive, antiallergic, anti-inflammatory, antimalarial, antipsychotic, cardioprotective, antifungal, antidepressant and antiviral. FDA approved many piperazine scaffold-based drugs for treatment various viral infections, therefore establishing pharmacological importance derivatives. Only few reviews on antiviral containing are available literature, despite its great medicinal significance. This review deals with agents covering literature reports from 2010-2023.

Language: Английский

Citations

8
Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors DOI Creative Commons
Xudong Wang,

Liwei Xiong,

Ying Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based 3-chymotrypsin-like protease (3CLpro, Nsp5) and papain-like (PLpro) domains of Nsp3, as well novel non-nucleoside nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking medicinal chemistry led development LU9, a nonpeptide 3CLpro inhibitor with an IC50 0.34 μM, LU10, whose crystal structure showed distinct binding mode within active site. X-ray cocrystal SARS-CoV-2 PLpro in complex XD5 uncovered previously unexplored site adjacent catalytic pocket. Additionally, Nsp12 XJ5 achieved potency 0.12 μM following comprehensive structure–activity relationship analysis optimization. Molecular dynamics revealed potential mode. These compounds offer valuable chemical probes target validation represent promising candidates antiviral therapies.

Language: Английский

Citations

2
Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 DOI Creative Commons
Ahmed H. Bakheit, Quaiser Saquib, Sarfaraz Ahmed

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(11), P. 2175 - 2175

Published: Oct. 30, 2023

COVID-19, a disease caused by SARS-CoV-2, has huge loss of human life, and the number deaths is still continuing. Despite lack repurposed drugs vaccines, search for potential small molecules to inhibit SARS-CoV-2 in demand. Hence, we relied on drug-like characters ten phytochemicals (compounds 1–10) that were previously isolated purified our research team from Saudi medicinal plants. We computationally evaluated inhibition RNA-dependent RNA polymerase (RdRp) compounds 1–10. Non-covalent (reversible) docking 1–10 with RdRp led formation hydrogen bond template primer nucleotides (A U) key amino acid residues (ASP623, LYS545, ARG555, ASN691, SER682, ARG553) its active pocket. Covalent (irreversible) revealed 7, 8, 9 exhibited their irreversible nature binding CYS813, crucial palm domain RdRP. Molecular dynamic (MD) simulation analysis RMSD, RMSF, Rg parameters affirmed RdRP complexes stable showed less deviation. Our data provide novel information demonstrated non-nucleoside interaction capabilities shed new scaffolds as antivirals against SARS-CoV-2.

Language: Английский

Citations

3