Effectiveness of Oral Nirmatrelvir/Ritonavir vs. Intravenous Three-Day Remdesivir in Preventing Progression to Severe COVID-19: A Single-Center, Prospective, Comparative, Real-Life Study

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1515 - 1515

Published: July 7, 2023

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted a tertiary care hospital, from 1 January 2022 until 15 March 2023, during prevalence Omicron variant. Inverse probability treatment weighting (IPTW) was used to account differences between groups. Results: We included 521, mainly (56%), our analysis; 356 (68.3%) received 3RDV 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) met primary end-point at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, choice did affect outcomes. In multivariable logistic regression we found that one (OR 0.26, 95%CI 0.07–0.99, 0.049) two 0.06, 0.01–0.55, 0.014) vaccine booster shots reduced risk adverse Conclusion: patient population high-risk, immunocompromised, vaccinated variant, were equally effective prevention death.

Language: Английский

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SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1144 - 1144

Published: March 4, 2024

The SARS-CoV-2 virus and its mutations have affected human health globally created significant danger for the of people all around world. To cure this virus, Angiotensin Converting Enzyme-2 (ACE2) receptor, main protease (Mpro), spike proteins were found to be likely candidates synthesis novel therapeutic drug. In past, capable engaging in interaction with a wide variety ligands, including both manmade plant-derived small molecules. Pyrus communis L., Ginko bibola, Carica papaya, Syrian rue, Pimenta dioica some plant species that studied their tendency interact (Mpro) research project (6LU7). This scenario investigates geometry, electronic, thermodynamic properties computationally. Assessing intermolecular forces phytochemicals targets Mpro protein (SP) resulted recognition compound, kaempferol, as most potent binding ligand, −7.7 kcal mol−1. Kaempferol interacted ASP-187, CYS-145, SER-144, LEU 141, MET-165, GLU-166 residues. Through additional molecular dynamic simulations, stability ligand–protein interactions was assessed 100 ns. remained intact 33% contact strength phenolic OH group. We noted change torsional conformation, dynamics simulation showed potential variation range from 3.36 7.44 against 45–50-degree angle rotation. SAR, pharmacokinetics, drug-likeness characteristic investigations kaempferol may suitable candidate serve model designing developing new anti-COVID-19 medicines.

Language: Английский

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SARS-CoV-2 replication and drug discovery

Molecular and Cellular Probes, Journal Year: 2024, Volume and Issue: 77, P. 101973 - 101973

Published: July 24, 2024

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) has killed millions of people and continues to wreak havoc across globe. This sudden deadly pandemic emphasizes necessity for anti-viral drug development that can be rapidly administered reduce morbidity, mortality, virus propagation. Thus, lacking efficient anti-COVID-19 treatment, especially given lengthy process as well critical death tool been associated with SARS-CoV-2 since its outbreak, repurposing (or repositioning) constitutes so far, ideal ready-to-go best approach in mitigating viral spread, containing infection, reducing COVID-19-associated rate. Indeed, based on molecular similarity previous coronaviruses (CoVs), repurposed drugs have reported hamper replication. Therefore, understanding inhibition mechanisms replication chemicals known block CoV multiplication is crucial, it opens way particular treatment options COVID-19 therapeutics. In this review, we highlighted basics underlying drug-repurposing strategies against SARS-CoV-2. Notably, discussed replication, involving including proteases (3C-like protease, 3CL

Language: Английский

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Synthesis, NMR spectroscopic characterization, DFT calculations, and molecular docking of new substituted phenolic and pyranopyran derivatives obtained from triacetic acid lactone

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141538 - 141538

Published: Jan. 1, 2025

Language: Английский

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Bird's eye view of natural products for the development of new anti‐HIV agents: Understanding from a therapeutic viewpoint

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Acquired immune deficiency syndrome (AIDS) is the name used to describe several potentially life-threatening infections and disorders that happen when HIV has severely compromised system. The primary effect of decrease host immunity, exposing external pathogens. development pharmaceutical drugs directly cure infection crucial because current wide-ranging epidemic HIV. Most therapeutic anti-HIV are nucleosides. However, their high toxicity potential for drug resistance restrict use. Many most effective clinical inhibit HIV, activation latent AIDS have been obtained from natural sources. This review focuses on medicinal products treating managing AIDS. Notwithstanding, further research studies needed understand subject its dynamics.

Language: Английский

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Investigating blood–brain barrier penetration and neurotoxicity of natural products for central nervous system drug development

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 3, 2025

Abstract Natural Products (NPs) are increasingly utilized worldwide for their potential therapeutic benefits, including central nervous system (CNS) disorders. Studies have shown açai berries mitigating Parkinson’s disease progression through dopaminergic neuroprotection via Nrf-2 HO-1 pathways. Ashwagandha, an evergreen shrub, has as a neurodegenerative disorders axonal regeneration in Aβ25-35-treated cortical neurons vitro. In most cases, promising NPs tested using vitro assays or simpler systems during the early stages of drug discovery. However, critical challenge lies lack data on blood-brain barrier (BBB) penetration, which is significant determinant successful development CNS drugs. Our first goal was to test our in-house NP constituent library Parallel Artificial Membrane Permeability Assay (PAMPA-BBB), with aim understanding BBB-penetration potential. Of constituents tested, 255 were found moderate high BBB permeability. next understand if these compounds could exhibit toxicity. Neuronal viability and neurite outgrowth performed this subset identify neurotoxicity Around 35% showed inhibition. The habitual widespread consumption underscores importance subjecting additional testing validation vivo ascertain detrimental effects. Understanding permeability assessing mechanisms will significantly benefit discovery community.

Language: Английский

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Activity of Sesquiterpene Lactones and Umbelliferone From Campovassouria cruciata on SARS‐CoV‐2 Replication and on the Release of Pro‐Inflammatory Cytokines in Lung Cells

Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

The investigation of natural products is a valid strategy to identify compounds active against coronaviruses. We herein report the screening Baccharis and Campovassouria plant species murine betacoronavirus hepatitis virus-3 (MHV-3), assays that can be carried out in BSL-2 facilities. These genera occur exclusively Americas are source secondary metabolites with antiviral anti-inflammatory activity. cruciata emerged as most from screening, its phytochemical afforded discovery new isomer leptocarpin, 3-epi-leptocapin (1), addition sesquiterpenes lactones leptocarpin (2) arturin (3), along umbelliferone (4). structures were elucidated by extensive mono- two-dimensional 1H 13C NMR data analysis. activity isolated was also assayed Calu-3 cells infected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All inhibited SARS-CoV-2 replication, reduction viral load approximately 1.7-2.0 log when tested at 7.5 µM. To evaluate potential activity, A549 stimulated IFN-γ TNF-α. Both 3-epi-leptocarpin (1) (4) interleukin-6 (IL-6) IL-8 release significantly. Compound 1 reduced production reactive oxygen (ROS) cells, assessed flow cytometry using DCFH-DA, whereas 4 exhibited ROS values seven-fold higher than basal level. Our results highlight C. promising bioactive compounds, which deserve future investigations explore their for development therapeutic agents inflammatory diseases.

Language: Английский

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Identification of Significant Mutations in Spike Protein of SARS‐CoV‐2 Variants of Concern and the Discovery of Potent Inhibitors

Global Health, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: SARS‐CoV‐2 is a positive‐sense single‐stranded RNA virus that has propensity for infecting epithelial cells and the respiratory system. The two important proteins, structural nonstructural make architecture of this virus. Aim: This research aimed at studying significant mutations in spike protein variants concern (VoCs) finding shared among omicron other four (alpha, beta, gamma, delta). purpose study was to draw comparisons between wild type mutant followed by identifying potent inhibitors (ligand) could be used against its latest VoC. Methodology: In research, we had studied 16 major as well (6) present region SARS‐CoV‐2. Subsequently, determined structure wild‐type from Protein Data Bank (PDB) with ID 7R4I. Furthermore, variant modeled SWISS‐MODEL. ligand dataset also collected literature different databases. Both proteins were docked database Molecular Operating Environment (MOE). docking analysis performed, best molecules, AZ_2 AZ_13, finalized based on their energy values, interactions, scores our proteins. Results: demonstrated score −6.1753 MOE, values −4.3889 −6.1753. It formed key hydrogen bond interactions. AZ_13 showed −5.9, −9.3 forming donor acceptor interactions Asp950 (3.06 Å), Ile312 (3.13 Glu309 (3.27 Å). These suggest strong binding affinity potential efficacy. Thus, work emphasized identification target‐based drug variant. Outcomes: Based computational it suggested proposed compound can remedy

Language: Английский

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Traditional Tibetan medicine to fight against COVID-19: Basic theory and therapeutic drugs

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

The Coronavirus Diseases 2019 (COVID-19) has been rapidly spreading globally and caused severe harm to the health of people a substantial social burden. In response this situation, experts around world have considered various treatments, including use traditional medicine. Traditional Tibetan medicine (TTM), one medicines in China, played an important role treatment infectious diseases history. It formed solid theoretical foundation accumulated rich experience diseases. review, we provide comprehensive introduction basic theory, strategies, commonly used drugs TTM for COVID-19. addition, efficacies potential mechanisms these against COVID-19 are discussed based on available experimental data. This review may information research, clinical application drug development or other More pharmacological studies needed reveal therapeutic active ingredients

Language: Английский

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Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411

Antiviral Research, Journal Year: 2023, Volume and Issue: 219, P. 105731 - 105731

Published: Oct. 12, 2023

Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment prevention SARS-CoV-2 infections pose a challenge. In search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from Baltic cyanobacterium Nostoc edaphicum tested against SARS-CoV-2. Of these depsipeptides, Arg-containing structural variants showed strongest inhibition Delta infection A549ACE2/TMPRSS2 cells. The functional assays indicated direct interaction CP978 with virions. also induced significant decline virus replication primary human airway epithelial cells (HAE). four variants, Wuhan, Alpha, Omicron Delta, only Wuhan was not affected by CP978. Finally, analyses application confocal microscopy pseudoviruses that CP978-mediated viral results binding cyanopeptolin coronaviral S protein. Considering potency mode action CP978, significance peptide as antiviral candidate should be further

Language: Английский

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