Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 228 - 228

Published: Jan. 19, 2023

Influenza is a contagious infection in humans that caused frequently by low pathogenic seasonal influenza viruses and occasionally avian (AIV) of H5, H7, H9 subtypes. Recently, the clinical sector poultry has been confronted with many challenges, including limited number antiviral drugs rapid evolution drug-resistant variants. Herein, anti-influenza activities various plant-derived phytochemicals were investigated against highly A/H5N1 virus (HPAIV H5N1) human A/H1N1 (LPHIV H1N1). Out 22 tested phytochemicals, steroid compounds β-sitosterol β-sitosterol-O-glucoside have very potent activity predefined A (IAV). Both steroids could induce such affecting multiple stages during IAV replication cycles, viral adsorption major significant impact on directly cell-free status "viricidal effect". On molecular level, several docking studies suggested exhibited viricidal effects through blocking active binding sites hemagglutinin surface protein, as well showing inhibitory neuraminidase M2 proton channel activity. The phytoestrogen structural similarity form female sex hormone estradiol, this likely one determinants enables its derivative to control vitro. This promising O-glycoside derivative, according both vitro cheminformatics studies, recommend for further going preclinical phases efficient drug candidates.

Language: Английский

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Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro , molecular docking, molecular dynamics, and SAR studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Jan. 26, 2023

Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, docking studies were used to investigate the binding interactions of 138 against human topoisomerase II-DNA complex. Followed by MD simulations 200 ns MM-GBSA calculations. On other hand, activities most candidates investigated three cell lines using doxorubicin (DOX) as reference drug. Notably, spiramycin (SP) clarithromycin (CL) showed anticancer potentials on MCF-7 line. Moreover, azithromycin (AZ) CL exhibited good HCT-116 Finally, TOP-2 enzyme inhibition assay was carried out confirm proposed rationale. Briefly, potent inhibitory recorded erythromycin (ER) roxithromycin (RO). Additionally, SAR study opened eyes pharmacophores encountered these antibiotics.HighlightsMolecular 139 complex.SP, RO, AZ, CL, ER commercially available candidates.Molecular dynamics five complexes.MM-GBSA calculations frontier complexes.SP line, besides, AZ line.Potent RO.

Language: Английский

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Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development

Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: April 26, 2024

About four years have passed since the detection of first cases COVID-19 in China. During this lethal pandemic, millions people lost their lives around world. Since waves infection, various pharmacotherapeutic agents been examined management COVID-19. Despite all these efforts pharmacotherapy, drug repurposing, and design development new drugs, multiple organ involvement complications occurred during Some became chronic long-lasting which led to "long COVID" syndrome appearance. Therefore, best way eradicate pandemic is prophylaxis through mass vaccination. In regard, vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA DNA vaccines), adenovirus-vectored protein-based subunit designed developed prevent or reduce hospitalization, mortality rates. focused review, at first, most commonly reported clinical presentations summarized. addition, different therapeutic regimens latest status listed. Furthermore, related signs, symptoms, mentioned. At end, effectiveness available with against early SARS-CoV-2 variants currently circulating interest (VOI) necessity booster shots summarized discussed more detail.

Language: Английский

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The Breadth of Bacteriophages Contributing to the Development of the Phage-Based Vaccines for COVID-19: An Ideal Platform to Design the Multiplex Vaccine

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1536 - 1536

Published: Jan. 12, 2023

Phages are highly ubiquitous biological agents, which means they ideal tools for molecular biology and recombinant DNA technology. The development of a phage display technology was turning point in the design phage-based vaccines. now recognized as universal adjuvant-free nanovaccine platforms. well-suited vaccine owing to their high stability harsh conditions simple inexpensive large-scale production. aim this review is summarize overall breadth antiviral therapeutic perspective phages contributing vaccines COVID-19. We show that induce strong specific humoral response by targeted particles carrying epitopes SARS-CoV-2. Further, engineering T4 bacteriophage CRISPR (clustered regularly interspaced short palindromic repeats) presents valuable platform with potential capabilities genetic plasticity, intrinsic immunogenicity, stability.

Language: Английский

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What’s new in flow biocatalysis? A snapshot of 2020–2022

Frontiers in Catalysis, Journal Year: 2023, Volume and Issue: 3

Published: April 21, 2023

Flow biocatalysis is a key enabling technology that increasingly being applied to wide array of reactions with the aim achieving process intensification, better control biotransformations, and minimization waste stream. In this mini-review, selected applications flow preparation food ingredients, APIs fat- oil-derived commodity chemicals, covering period 2020-2022, are described.

Language: Английский

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Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 5, 2024

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the via hijacking essential machinery components to evade provoked antiviral innate immunity against invading pathogen. Respiratory infections are usually acute with ability activate pattern (PRRs) in/on cells, resulting production release interferons (IFNs), proinflammatory cytokines, chemokines, IFN-stimulated genes (ISGs) reduce fitness mitigate infection. Nevertheless, game between is a complicated dynamic process, which they restrict each other specific factors maintain their own advantages win this game. The primary role non-structural protein 1 (NS1 Nsp1) influenza A (IAV) pandemic severe respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, control host-induced immune responses. This review provides comprehensive overview genesis, spatial structure, cellular interactors, mechanisms underlying unique biological functions IAV NS1 SARS-CoV-2 Nsp1 infected cells. We also highlight both proteins modulating replication pathogenicity. Eventually, because important during infection, we describe promising potential as targets for therapy development live attenuated vaccines (LAV). Conclusively, play an virus–host interactions, replication, pathogenesis, pave way develop novel prophylactic and/or therapeutic interventions treatment these human pathogens.

Language: Английский

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MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 28, 2023

SARS-CoV-2 infection has led to several million deaths worldwide and ravaged the economies of many countries. Hence, developing therapeutics against remains a core priority in fight COVID-19. Most drugs that have received emergency use authorization for treating exhibit number limitations, including side effects questionable efficacy. This challenge is further compounded by reinfection after vaccination high likelihood mutations, as well emergence viral escape mutants render spike glycoprotein-targeting vaccines ineffective. Employing de novo drug synthesis or repurposing discover broad-spectrum antivirals target highly conserved pathways within machinery focus current research. In recent study, masitinib, clinically safe human coronavirus OC43 (HCoV-OC43), was identified an antiviral agent with effective inhibitory activity 3CLpro. Masitinib currently under clinical trial combination isoquercetin hospitalized patients (NCT04622865). Nevertheless, masitinib kinase-related effects; hence, development analogs lower anti-tyrosine kinase becomes necessary. this attempt address limitation, we executed comprehensive virtual workflow silico drug-like compounds matching selected pharmacophore features 3CLpro-bound state masitinib. We novel lead compound, "masitinibL", analog demonstrated strong properties addition, masitinibL displayed low selectivity tyrosine kinases, which strongly suggests promising therapeutic preferable

Language: Английский

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Optical, Structural, Electrical Characterization of (Polyvinyl Alcohol–Carboxymethyl Cellulose-Manganese Dioxide) Nanocomposite Fabricated via Laser Ablation

Journal of Inorganic and Organometallic Polymers and Materials, Journal Year: 2022, Volume and Issue: 32(8), P. 2863 - 2872

Published: April 1, 2022

Language: Английский

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Theoretical effectiveness of steam inhalation against SARS-CoV-2 infection: updates on clinical trials, mechanism of actions, and traditional approaches

Heliyon, Journal Year: 2022, Volume and Issue: 8(1), P. e08816 - e08816

Published: Jan. 1, 2022

Steam inhalation therapy can be a contemporary approach for COVID-19 affected patients of all age groups to manage respiratory conditions, though it presently lacks the scientific backing establish itself as befitting practice. The has facilitated this traditional home remedy resurface among general mass helpful prevention and adjuvant treatment disease. In review, means SARS-CoV-2 infection impact parameters, namely steam heat on such been delineated via enumerating effect parameters in human body against SARS-CoV-2. literature search was conducted using PubMed, Web Science, Scopus, ScienceDirect, Wiley Online Library, Google Scholar, CNKI Scholar databases. keywords used survey include 'Steam inhalation', 'SARS-CoV-2', 'COVID-19', 'Clinical study', 'Mechanism action', 'Traditional uses', 'Phytochemistry' 'Adverse effects'. Clinical studies concerning by have comprehended demarcate obscurity safety profile procedure also outlined emphasizing evading measures other related disease states. To recapitulate, application with herbal concoctions phytochemicals having folkloric prevalence an inhalable illnesses explored review work focus new aspect paradigm progress further research hither.

Language: Английский

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Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11861 - 11861

Published: Oct. 6, 2022

The search for an effective anti-viral to inhibit COVID-19 is a challenge the specialized scientific research community. This work investigated anti-coronavirus activity spirooxindole-based phenylsulfone cycloadducts in single and combination protocols. newly designed anti-SARS-CoV-2 therapeutics spirooxindoles synthesized by [3 + 2] cycloaddition reactions represent efficient approach. One-pot multicomponent between phenyl vinyl sulfone, substituted isatins, amines afforded highly stereoselective with three stereogenic centers. Herein, were assessed individually against pathogenic human coronaviruses proved be potent safer. Interestingly, synergistic effect combining potent, tested resulted improved antiviral as well better host-cell safety. Compounds 4i 4d represented most MERS-CoV IC50 values of 11 23 µM, respectively. Both compounds 4c 4e showed equipotent best SARS-CoV-2 17 18 respectively, then 4k 24 27 Then, our attention oriented perform protocol different binding mode accompanied pharmacophores. Combination compound more active displayed = 3.275 µM half maximal cytotoxic-concentration CC50 11832 µM. MD simulation potential silico ADMET properties investigated. study highlights drug-like cocktail protocol.

Language: Английский

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