43,668 results match your criteria compounds ligands

Modulators of Immunoregulatory Exonucleases PLD3 and PLD4 Identified by High-Throughput Screen.

Bioorg Med Chem Lett 2021 Jul 28:128293. Epub 2021 Jul 28.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States. Electronic address:

PLD3 and PLD4 have recently been revealed to be endosomal exonucleases that regulate the innate immune response by digesting the ligands of nucleic acid sensors. These enzymes can suppress RNA and DNA innate immune sensors like toll-like receptor 9, and PLD4-deficent mice exhibit inflammatory disease. Targeting these immunoregulatory enzymes presents an opportunity to indirectly regulate innate immune nucleic acid sensors that could yield immunotherapies, adjuvants, and nucleic acid drug stabilizers. Read More

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In silico screening of neurokinin receptor antagonists as a therapeutic strategy for neuroinflammation in Alzheimer's disease.

Mol Divers 2021 Jul 31. Epub 2021 Jul 31.

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.

Neuroinflammation is one of the detrimental factors leading to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. The activation of microglial neurokinin 1 receptor (NK1R) by substance P (SP) enhances neuroinflammation which is mediated through pro-inflammatory pathways involving NFkB, ERK1/2, and P38 and thus projects the scope and importance of NK1R inhibitors. Emphasizing the inhibitory role of N Acetyl L Tryptophan (L-NAT) on NK1R, this is the first in silico screening of L-NAT mediated NK1R antagonism. Read More

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GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark;

Ca/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) is a key neuronal signaling protein and an emerging drug target. The central hub domain regulates the activity of CaMKIIα by organizing the holoenzyme complex into functional oligomers, yet pharmacological modulation of the hub domain has never been demonstrated. Here, using a combination of photoaffinity labeling and chemical proteomics, we show that compounds related to the natural substance γ-hydroxybutyrate (GHB) bind selectively to CaMKIIα. Read More

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Adsorption performance and kinetic study of hierarchical porous Fe-based MOFs for toluene removal.

Sci Total Environ 2021 Jun 22;793:148622. Epub 2021 Jun 22.

Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

In light of the promising merits of large surface area, uniform pore size, and tunable functional groups, metal-organic frameworks (MOFs) have great potential to be utilized for adsorbing volatile organic compounds (VOCs). In this study, three Fe-based MOFs, MIL-100(Fe), MIL-101(Fe), and MIL-53(Fe), were synthesized systematically and used to adsorb a typical VOC, toluene. Static adsorption, dynamic breakthrough curves, and adsorption kinetics were conducted to assess the adsorption performance. Read More

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Quantum simulations of SARS-CoV-2 main protease M enable high-quality scoring of diverse ligands.

J Comput Aided Mol Des 2021 Jul 30. Epub 2021 Jul 30.

Quantum Simulation Technologies, Inc, 625 Massachusetts Ave, Floor 2, Cambridge, MA, 02139, USA.

The COVID-19 pandemic has led to unprecedented efforts to identify drugs that can reduce its associated morbidity/mortality rate. Computational chemistry approaches hold the potential for triaging potential candidates far more quickly than their experimental counterparts. These methods have been widely used to search for small molecules that can inhibit critical proteins involved in the SARS-CoV-2 replication cycle. Read More

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Noncovalent axial I∙∙∙Pt∙∙∙I interactions in platinum(II) complexes strengthen in the excited state.

Chemphyschem 2021 Jul 30. Epub 2021 Jul 30.

University of Jyväskylä, Department of Chemistry, P.O. Box 35, 40014, Jyväskylä, FINLAND.

Coordination compounds of platinum(II) participate in various noncovalent axial interactions involving metal center. Weakly bound axial ligands can be electrophilic or nucleophilic; however, interactions with nucleophiles are compromised by electron density clashing. Consequently, simultaneous axial interaction of platinum(II) with two nucleophilic ligands is almost unprecedented. Read More

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Bis(N-picolinamido)cobalt(II) Complexes Display Antifungal Activity toward Candida albicans and Aspergillus fumigatus.

ChemMedChem 2021 Jul 29. Epub 2021 Jul 29.

School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.

This report highlights the synthesis and characterization of ten new bis(N-picolinamido)cobalt(II) complexes of the type [(L) CoX ] , whereby L=N-picolinamide ligand and X=diisothiocyanato (-NCS), dichlorido (-Cl) or diaqua (-OH ) ligands. Single crystal X-ray (SC-XRD) analysis for nine of the structures are reported and confirm the picolinamide ligand is bound to the Co(II) center through a neutral N,O binding mode. With the addition of powder X-ray diffraction (PXRD), we have confirmed the cis and trans ligand arrangements of each complex. Read More

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Biomimetic estrogen sensor based on soft colloidal probes.

Biosens Bioelectron 2021 Jul 15;192:113506. Epub 2021 Jul 15.

Institute of Biochemistry, Leipzig University, Johannisallee 21 - 23, 04103, Leipzig, Germany.

An increasing number of reports substantiate the link between emerging estrogenic pollutants and a variety of adverse effects including developmental disorders, infertility, cancer and neurological disorders, threatening public health as well as environment. The detection of the diverse classes of estrogenic and antiestrogenic substances is still challenging due to analytics which needs to cover the whole range of compounds acting on estrogen receptors and the complex estrogen pathways. In this proof-of-concept study, we report a novel biomimetic detection scheme based on the specific recognition of estrogenic ligands by estrogen sulfotransferase 1E1 (SULT1E1), which acts as one of the key enzymes in estrogen homeostasis. Read More

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Metabolic benefits of novel histamine H receptor ligands in the model of excessive eating: The importance of intrinsic activity and pharmacokinetic properties.

Biomed Pharmacother 2021 Jul 26;142:111952. Epub 2021 Jul 26.

Department of Pharmacological Screening, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Cracow, Poland. Electronic address:

Aims: One of the therapeutic approaches in the treatment of obesity is the use of histamine H receptor ligands. Histamine plays a significant role in eating behavior because it causes a loss of appetite and is considered to be a satiety signal released during food intake.

Material And Methods: Histamine ligands were selected based on the preliminary studies which included determination of intrinsic activity and selected pharmacokinetic parameters. Read More

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Lateral Metallation and Redistribution Reactions of Sodium Ferrates Containing Bulky 2,6-Diisopropyl-N-(trimethylsilyl)anilide Ligands.

Chemistry 2021 Jul 29. Epub 2021 Jul 29.

Universitat Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012, Bern, SWITZERLAND.

Alkali-metal ferrates containing amide groups have emerged as regioselective bases capable of promoting Fe-H exchanges of aromatic substrates. Advancing this area of heterobimetallic chemistry, a new series of sodium ferrates is introduced incorporating the bulky arylsilyl amido ligand N(SiMe3)(Dipp) (Dipp= 2,6-iPr2-C6H3). Influenced by the large steric demands imposed by this amide, transamination of [NaFe(HMDS)3] (HMDS = N(SiMe3)2) with an excess of HN(SiMe3)(Dipp) led to the isolation of heteroleptic [Na(HMDS)2Fe{N(SiMe3)Dipp}]∞ (1) resulting from the exchange of just one HMDS  group. Read More

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Poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith with bonded octadecyl ligands for use in reversed-phase capillary electrochromatography.

Electrophoresis 2021 Jul 29. Epub 2021 Jul 29.

Department of Chemistry, Oklahoma State University, Stillwater, OK, 74078-3071, USA.

A carboxy precursor monolithic column, namely poly(carboxy ethyl acrylate-co-ethylene glycol dimethacrylate was first produced in a 100 μm i.d. fused-silica capillary and subsequently surface bonded with n-octadecyl (C ) ligands by a post-polymerization functionalization process with octadecylamine in the presence of N,N´-dicyclohexylcarbodiimide. Read More

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Synthesis and Identification of Novel Potential Molecules Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach.

Appl Biochem Biotechnol 2021 Jul 29. Epub 2021 Jul 29.

Laboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétences Pharmaco-Chimie, Faculté Des Sciences, Université Mohammed V, BP 10014, Rabat, Morocco.

The novel coronavirus disease that arises in the end of 2019 (COVID-19) in Wuhan, China, has rapidly spread over the globe and was considered as a world pandemic. Currently, various antiviral therapies or vaccines are available, and many researches are ongoing for further treatments. Targeting the coronavirus' main protease (key enzyme: 3CLpro) is growing in importance in anti-SARS-CoV-2 drug discovery process. Read More

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The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study.

PeerJ 2021 19;9:e11590. Epub 2021 Jul 19.

College of Applied Science, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia.

The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. Read More

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Neuroinflammation and psychiatric disorders: relevance of C1q, translocator protein (18 kDa) (TSPO), and neurosteroids.

World J Biol Psychiatry 2021 Jul 29:1-20. Epub 2021 Jul 29.

Experimental Neuropharmacology, Department of Anesthesiology, Technische Universität München, Munich, Germany.

There is increasing evidence that neuroinflammatory processes may play a role in the pathophysiology of psychiatric disorders. Recently, the complement protein C1q and the translocator protein (18 kDa) (TSPO) have attracted considerable interest in this context. C1q is a small molecule which is involved into synaptic pruning mechanisms, increases during aging and may contribute to neurodegenerative disorders. Read More

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Anti-quorum sensing potential of ketoprofen and its derivatives against Pseudomonas aeruginosa: insights to in silico and in vitro studies.

Arch Microbiol 2021 Jul 28. Epub 2021 Jul 28.

Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Antibiotics are usually used for the treatment of bacterial infections, but multidrug-resistant strains are a phenomenon that has been growing at an increasing rate worldwide. Thus, there is an increasing need for novel strategies for combatting infectious diseases. Many pathogenic bacteria apply quorum sensing (QS) to regulate their pathogenicity and virulence factors production. Read More

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Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells.

Oncotarget 2021 Jul 20;12(15):1444-1456. Epub 2021 Jul 20.

Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Telomerase/telomere-targeting therapy is a potentially promising approach for cancer treatment because even transient telomere dysfunction can induce chromosomal instability (CIN) and may be a barrier to tumor growth. We recently developed a dual-HAC (Human Artificial Chromosome) assay that enables identification and ranking of compounds that induce CIN as a result of telomere dysfunction. This assay is based on the use of two isogenic HT1080 cell lines, one carrying a linear HAC (containing telomeres) and the other carrying a circular HAC (lacking telomeres). Read More

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Combined molecular docking and dynamics simulations studies of natural compounds as potent inhibitors against SARS-CoV-2 main protease.

J Biomol Struct Dyn 2021 Jul 27:1-10. Epub 2021 Jul 27.

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

Main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-2 the new strain of coronavirus. In this study, we evaluated biologically active compounds present in medicinal plants as potential SARS-CoV-2 Mpro inhibitors, using a molecular docking study with Autodock Vina software. Top seven compounds , , , , and among 50 molecules of natural Origin (Algerian Medicinal plants) were selected which had better and significantly low binding energy as compared to the reference molecule with binding affinities of -9. Read More

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The Induction Mechanism of the Flavonoid-Responsive Regulator FrrA.

FEBS J 2021 Jul 27. Epub 2021 Jul 27.

Institute for Biochemistry, Dept. Molecular Structural Biology, University of Greifswald, Greifswald, Germany.

Bradyrhizobium diazoefficiens, a bacterial symbiont of soybean and other leguminous plants, enters a nodulation-promoting genetic programme in the presence of host-produced flavonoids and related signalling compounds. Here, we describe the crystal structure of an isoflavonoid-responsive regulator (FrrA) from Bradyrhizobium, as well as co-crystal structures with inducing and non-inducing ligands (genistein and naringenin, respectively). The structures reveal a TetR-like fold whose DNA-binding domain is capable of adopting a range of orientations. Read More

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Rational Multitargeted Drug Design Strategy from the Perspective of a Medicinal Chemist.

J Med Chem 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, P. R. China.

The development of multitarget-directed ligands (MTDLs) has become a widely focused research topic, but rational design remains as an enormous challenge. This paper reviews and discusses the design strategy of incorporating the second activity into an existing single-active ligand. If the binding sites of both targets share similar endogenous substrates, MTDLs can be designed by merging two lead compounds with similar functional groups. Read More

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Au···H-C Hydrogen Bonds as Design Principle in Gold(I) Catalysis.

Angew Chem Int Ed Engl 2021 Jul 27. Epub 2021 Jul 27.

Ruhr-Universitat Bochum, Fakultät für Chemie und Biochemie, Universitätsstraße 150, 44780, Bochum, GERMANY.

Secondary ligand metal interactions are decisive in many catalytic transformations. While arene-gold interactions have repeatedly been reported as critical structural feature in many high-performance gold catalysts, we herein report that these interactions can also be replaced by Au···H-C hydrogen bonds without suffering any reduction in catalytic performance. Systematic experimental and computational studies on a series of ylide-substituted phosphines featuring either a PPh 3 ( Ph YPhos) or PCy 3 ( Cy YPhos) moiety showed that the arene-gold interaction in the aryl-substituted compounds is efficiently compensated by the formation of Au···H-C hydrogen bonds. Read More

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In silico studies of Potency and safety assessment of selected trial drugs for the treatment of COVID-19.

In Silico Pharmacol 2021 22;9(1):45. Epub 2021 Jul 22.

Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.

SARS-CoV-2 has caused millions of infections and hundreds of thousands of deaths globally. Presently, no cure for SARS-CoV-2 infection is available; thus, all hands are on deck for new drug discovery. Although, several studies have reported the potentials of some already approved drugs for the treatment of COVID-19. Read More

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Natural multi-target modulators of pathological pathways in Alzheimer's disease isolated from the skin.

Nat Prod Res 2021 Jul 27:1-5. Epub 2021 Jul 27.

Laboratorio de Péptidos Bioactivos, Departamento de Química Orgánica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

The skin of anuran amphibians is a rich source of compounds with great medicinal potential. Alzheimer's disease (AD) is a complex disease associated with numerous pathological pathways, making their simultaneous modulation necessary. Nowadays the development of anti-AD drugs is focused on a Multi-Target Directed Ligands strategy. Read More

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6,6'-Ditriphenylamine-2,2'-bipyridine: Coordination Chemistry and Electrochemical and Photophysical Properties.

Inorg Chem 2021 Jul 27. Epub 2021 Jul 27.

Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.

A 2,2'-bipyridine with bulky triphenylamine substituents in the 6 and 6' positions of the ligand (6,6'-ditriphenylamine-2,2'-bipyridine, 6,6'-diTPAbpy) was generated. Despite the steric bulk, the ligand readily formed bis(homoleptic) complexes with copper(I) and silver(I) ions. Unfortunately, efforts to use the 6,6'-diTPAbpy system to generate heteroleptic [Cu(6,6'-diTPAbpy)(bpy)] complexes were unsuccessful with only the [Cu(6,6'-diTPAbpy)](PF) complex observed. Read More

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Tight-Binding Approach to Pyrazine-Mediated Superexchange in Copper-Pyrazine Antiferromagnets.

Inorg Chem 2021 Jul 26. Epub 2021 Jul 26.

School of Mathematics and Physics, The University of Queensland, St Lucia, Queensland 4072, Australia.

We investigate the cause of spatial superexchange anisotropy in a family of copper-based, quasi-two-dimensional materials with very similar geometries. The compounds in this family differ mainly in their inter-layer separation but they have very different magnetic interactions, even within the basal plane. We use density functional theory and Wannier functions to parameterize two complimentary tight-binding models and show that the superexchange between the Cu ions is dominated by a σ-mediated interaction between hybrid Cu-pyrazine orbitals centered on the copper atoms. Read More

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AIE-Active Difluoroboron Complexes with N,O-Bidentate Ligands: Rapid Construction by Copper-Catalyzed C-H Activation.

Adv Sci (Weinh) 2021 Jul 26:e2101814. Epub 2021 Jul 26.

Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, Münster, 48149, Germany.

The development of organic materials with high solid-state luminescence efficiency is highly desirable because of their fundamental importance and applicability in optoelectronics. Herein, a rapid construction of novel BF complexes with N,O-bidentate ligands by using Cu(BF ) •6H O as a catalyst and BF source is disclosed, which avoids the need for pre-composing the N,O-bidentate ligands and features a broad substrate scope and a high tolerance level for sensitive functional groups. Moreover, molecular oxygen is employed as the terminal oxidant in this transformation. Read More

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Direct Observation of Diastereomeric α-C-Bound Enolates during Enantioselective α-Arylations: Synthesis, Characterization, and Reactivity of Arylpalladium Fluorooxindole Complexes.

J Am Chem Soc 2021 Jul 26. Epub 2021 Jul 26.

Department of Chemistry, University of California, Berkeley, California 94702, United States.

The Pd-catalyzed asymmetric α-arylation of carbonyl compounds is a valuable strategy to form benzylic stereocenters. However, the origin of the stereoselectivity of these reactions is poorly understood, and little is known about the reactivity of the putative diastereomeric arylpalladium enolate intermediates. To this end, we report the synthesis and characterization of a series of diphosphine-ligated arylpalladium fluoroenolate complexes, including complexes bearing a metal-bound, stereogenic carbon and an enantioenriched chiral diphosphine ligand. Read More

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Improving the Solubility of Hexanuclear Heterometallic Extended Metal Atom Chain Compounds in Nonpolar Solvents by Introducing Alkyl Amine Moieties.

ACS Omega 2021 Jul 7;6(28):18487-18503. Epub 2021 Jul 7.

Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan.

The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) interaction at the d orbital between two kinds of metal complex is useful for obtaining heterometallic one-dimensional (1D) chains as well as heterometallic metal string compounds (HMSCs). Platinum dinuclear complexes, [Pt(piam)(NHR)]X (piam = pivalamidate, R = CH, CH, CH, or CH, X = anion), comprising σ* as HOMO were mixed with [Rh(OCCH)] comprising σ* as LUMO in solvents to afford single crystals of [{Rh(OCCH)}{Pt(piam)(NHR)}]X (-). Single-crystal X-ray analyses revealed that - are hexanuclear complexes that are one-dimensionally aligned as Pt-Pt-Rh-Rh-Pt-Pt with metal-metal bonds, where the alkyl moieties at end Pt atoms obstruct further 1D extension. Read More

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Repurposing FDA-approved drugs against multiple proteins of SARS-CoV-2: An study.

Sci Afr 2021 Sep 11;13:e00845. Epub 2021 Jul 11.

Genetics, Genomics and Bioinformatics Department, National Biotechnology Development Agency, Abuja, Nigeria.

The current crisis of the COVID-19 pandemic around the world has been devastating as many lives have been lost to the novel SARS CoV-2 virus. Thus, there is an urgent need for the right therapeutic drug to curb the disease. However, there is time constraint in drug development, hence the need for drug repurposing approach, a relatively fast and less expensive alternative. Read More

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September 2021

Discovery of Taroxaz-104: The First Potent Antidote of SARS-CoV-2 VOC-202012/01 Strain.

Amgad M Rabie

J Mol Struct 2021 Jul 16:131106. Epub 2021 Jul 16.

Dr. Amgad Rabie's Research Lab. for Drug Discovery (DARLD), Mansoura, Egypt.

Polyhydroxyphenols and nitrogenous heterocyclics are two of the most powerful active species of molecules in pharmaceutical chemistry, as each of them is renowned for its various bioactivities for humans. One of their outstanding actions is the antiviral activities, which clearly appear if the principal functional entities of both classes meet into one compound. The recent COVID-19 pandemic pushed us to computationally sift and assess our small library of synthetic 2-(3,4,5-trihydroxyphenyl)-1,3,4-oxadiazoles against the main coronaviral protein/enzymatic targets. Read More

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investigation to identify potential small molecule inhibitors of the RNA-dependent RNA polymerase (RdRp) nidovirus RdRp-associated nucleotidyltransferase domain.

Chem Phys Lett 2021 Sep 12;779:138889. Epub 2021 Jul 12.

Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) is a promising target for antiviral drugs. In this study, a chemical library (n = 300) was screened against the nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain. Blind docking was performed using a selection of 30 compounds and nine ligands were chosen based on their docking scores, safety profile, and availability. Read More

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September 2021