Synthesis of New Organoselenium-Based Succinanilic and Maleanilic Derivatives and In Silico Studies as Possible SARS-CoV-2 Main Protease Inhibitors

Inorganics, Journal Year: 2023, Volume and Issue: 11(8), P. 321 - 321

Published: July 29, 2023

Herein we report the synthesis of organic selenide-based maleanilic and succinanilic acids in good yields (up to 95%). Their structural identities were elucidated by spectroscopic techniques (e.g., IR, 1H- & 13C-NMR, MS). The ADMET analysis, molecule electrostatic potential map, DFT, frontier molecular orbital used study organoselenium compounds’ pharmacokinetics, drug-likeness characteristics, geometries, chemical electronic properties. Moreover, a docking tool was employed investigate selenides’ ability inhibit SARS-CoV-2 Mpro target (PDB: 7BFB). Within this context, selenides exhibited promising binding affinities receptor following order (12 > 11 10 9 7 8). Furthermore, dynamics simulations also carried out for 200 ns evaluate exact behavior most active compound (12) within pocket compared with its co-crystallized inhibitor (Co).

Language: Английский

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Nucleoside‐Based Drug Target with General Antimicrobial Screening and Specific Computational Studies against SARS‐CoV‐2 Main Protease

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(15)

Published: April 15, 2024

Abstract This review article aims to significantly advance the scientific community's efforts develop effective nucleoside‐based drugs for treating severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 ) and other emerging infectious diseases. study concentrates on main viral protease (Mpro) explores compounds as potential therapeutic agents. investigation investigated impact of acylation‐induced modifications nucleoside hydroxyl group subsequent properties. Nucleoside analogs, which are recognized their diverse biochemical properties, were synthesized rigorously screened evaluate antimicrobial efficacy. In domain pharmaceutical research, computational pharmacokinetics has emerged a critical tool, especially in pursuit analogs therapeutics. silico methods aid predicting pharmacokinetic traits, interactions with crucial enzymes, stability these biological environments, thereby streamlining drug design reducing experimental costs. Concurrently, studies revealed intricate between active site protease. The amalgamation screening insights underscores emergence potent candidates inhibitory activity against SARS‐CoV‐2 M pro . Additionally, this integrates that provide valuable into SARS‐CoV‐2.

Language: Английский

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The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8283 - 8283

Published: July 27, 2022

The vascular endothelium has several important functions, including hemostasis. homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins fibrinolytic antifibrinolytic ones. Coagulopathies are characterized by mutation-induced alteration the function certain coagulation factors or disturbed mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement nonreplacement treatments administration agents. Rebalancing products reestablish inhibiting natural pathways. These agents include monoclonal antibodies, such as concizumab marstacimab, which target tissue factor pathway inhibitor; interfering RNA therapies, fitusiran, targets antithrombin III; protease inhibitors, serpinPC, active protein C. In cases thrombophilia (deficiency C, S, V Leiden), treatment may direct oral anticoagulants, therapy (plasma recombinant ADAMTS13) congenital deficiency ADAMTS13, immunomodulators (prednisone) if autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) used context severe thrombophilia, regardless cause disorder. disseminated intravascular coagulation, choice consists antifibrinolytics, all-trans-retinoic acid, soluble human thrombomodulin.

Language: Английский

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In vitroand computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-M^Proinhibitors

RSC Advances, Journal Year: 2022, Volume and Issue: 12(41), P. 26895 - 26907

Published: Jan. 1, 2022

An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro). With objective targeting this receptor, a novel set pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines with terminal carboxamide fragments was designed, synthesized, and considered as an initial motif creation effective pan-coronavirus inhibitors. Accordingly, nine derivatives (21-29) have been introduced in vitro assay to evaluate their antiviral activity cytotoxicity effect against virus using Vero cells. The obtained data revealed that majority these showed potent cellular anti-COVID-19 prevent viral growth by more than 90% at two different concentrations weak or even no detectable cytotoxic on Extensive molecular docking simulations highlighted proper non-covalent interaction new compounds within binding pocket Mpro potential activity. In all synthesized indicated 25 29 promising inhibitory IC50 values low micromolar concentrations. dynamic simulation results predicted stability compound cavity hence supported high shown assay. These suggested merit further investigations drug candidates management SARS-CoV-2.

Language: Английский

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Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 135, P. 106390 - 106390

Published: Jan. 28, 2023

Language: Английский

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Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (M^pro) and Papain-like Protease (PL^pro)

Journal of Chemical Information and Modeling, Journal Year: 2023, Volume and Issue: 63(7), P. 2226 - 2239

Published: March 23, 2023

The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. main protease of (Mpro) and the papain-like (PLpro) are essential for viral replication key targets therapeutic development. In this work, we investigate mechanisms inhibition by diphenyl diselenide (PhSe)2 which is an archetypal model diselenides a renowned potential agent. in vitro inhibitory concentration against Vero E6 cells falls low micromolar range. Molecular dynamics (MD) simulations density functional theory (DFT) calculations [level theory: SMD-B3LYP-D3(BJ)/6-311G(d,p), cc-pVTZ] used inspect non-covalent modes both proteases via π-stacking mechanism covalent + Mpro product formation involving catalytic residue C145, respectively. CC50 (24.61 μM) EC50 (2.39 data indicate that good inhibitor virus cell culture model. silico findings proteases' (PhSe)2; particular, results here discussed Mpro, whose thermodynamics approximatively isoergonic, prompt further investigation design antiviral organodiselenides.

Language: Английский

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Nirmatrelvir exerts distinct antiviral potency against different human coronaviruses

Antiviral Research, Journal Year: 2023, Volume and Issue: 211, P. 105555 - 105555

Published: Feb. 14, 2023

Nirmatrelvir is the main component of Paxlovid, an oral antiviral drug approved for treatment COVID-19 caused by SARS-COV-2 infection. targets protease (Mpro), which substantially conserved among different coronaviruses. Here, our molecular docking analysis indicates comparable affinity nirmatrelvir binding to Mpro enzymes SARS-CoV-2 and three seasonal coronaviruses (OC43, 229E NL63). However, in cell culture models, we found that potently inhibited SARS-CoV-2, OC43 229E, but not NL63. The insensitivity NL63 was demonstrated at both viral replication infectious titer levels. activity against further confirmed human airway organoids. combination molnupiravir exerted differential patterns response 229E. These results revealed disparities ability inhibit coronaviruses, caution repurposing as a pan-coronavirus treatment.

Language: Английский

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Phenolic Compounds in Salicornia spp. and Their Potential Therapeutic Effects on H1N1, HBV, HCV, and HIV: A Review

Molecules, Journal Year: 2023, Volume and Issue: 28(14), P. 5312 - 5312

Published: July 10, 2023

Despite public health risk mitigation measures and regulation efforts by many countries, regions, sectors, viral outbreaks remind the world of our vulnerability to biological hazards importance actions. The saltwater-tolerant plants in Salicornia genus belonging Amaranthaceae family are widely recognized researched as producers clinically applicable phytochemicals. contain flavonoids, flavonoid glycosides, hydroxycinnamic acids, including caffeic acid, ferulic chlorogenic apigenin, kaempferol, quercetin, isorhamnetin, myricetin, isoquercitrin, myricitrin, which have all been shown support antiviral, virucidal, symptom-suppressing activities. Their potential pharmacological usefulness therapeutic medicine against infections has suggested studies, where recent studies suggest these phenolic compounds may infections. This study reviews antiviral effects, mechanisms action, agents aforementioned found spp. an influenza A strain (H1N1), hepatitis B C (HBV/HCV), human immunodeficiency virus 1 (HIV-1), no other literature described effects from at time publication. review a significant societal impact proposing development new nutraceuticals pharmaceuticals derived phenolic-rich formulations edible These could be utilized novel strategy combat pandemics caused H1N1, HBV, HCV, HIV-1. findings this indicate that myricitrin exhibit high efficiency inhibiting Myricetin exhibits inhibition H1N1 plaque formation reverse transcriptase, well integrase integration cleavage. Isoquercitrin shows excellent neuraminidase inhibition. Myricitrin inhibits HIV-1 infected cells. Extracts biomass contribute more effective efficient and, ultimately, improve health.

Language: Английский

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Molecular Dynamics Simulation of Ligands from Anredera cordifolia (Binahong) to the Main Protease (Mpro) of SARS-CoV-2

Journal of Tropical Medicine, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 13

Published: Nov. 22, 2022

COVID-19 in Indonesia is considered to be entering the endemic phase, and population expected live side by with SARS-CoV 2 viruses their variants. In this study, procyanidin, oleic acid, methyl linoleic vitexin, four compounds from binahong leaves-tropical/subtropical plant, were examined for interactions major protease (Mpro) of virus. Molecular dynamics simulation shows that procyanidin vitexin have best docking scores −9.132 −8.433, respectively. also Root Mean Square Displacement (RMSD) Fluctuation (RMSF) performance due dominant hydrogen, hydrophobic, water bridge interactions. However, further strain energy calculation obtained ligand torsion analyses, do not conform as much quercetin control even though these two ligands good terms interaction target protein.

Language: Английский

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Computational investigation of natural compounds as potential main protease (Mpro) inhibitors for SARS-CoV-2 virus

Computers in Biology and Medicine, Journal Year: 2022, Volume and Issue: 151, P. 106318 - 106318

Published: Nov. 18, 2022

Language: Английский

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