Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients

Medical Science Monitor, Journal Year: 2022, Volume and Issue: 28

Published: Jan. 1, 2022

On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from Medicines and Healthcare Products Regulatory Agency (MHRA) in UK. Molnupiravir is an orally bioavailable use at home when a SARS-CoV-2 test positive. 22nd December 2022, FDA granted emergency authorization (EUA) drug, nirmatrelvir/ritonavir (Paxlovid®) adults children with mild moderate COVID-19 increased risk of progression to severe COVID-19. These approvals come crucial time new variants concern virus are spreading rapidly. Although approved remdesivir (Veklury®) on October 2020 treatment requiring hospitalization, its has been limited by requirement intravenous administration healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, casirivimab costly also require medically-supervised administration. availability effective, low-cost drugs available community setting that can be used early stage infection now priority controlling An increasing number repurposed currently under investigation or stages approval. This Editorial aims present update current status treatments infection.

Language: Английский

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Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(8), P. 2892 - 2892

Published: April 15, 2023

Sepsis is currently defined as a life-threatening organ dysfunction caused by dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock subset of sepsis persistent hypotension, hospital mortality rates are higher than 40%. Although early has greatly improved in the past few years, patients who survive hyperinflammation subsequent damage often die from long-term complications, such secondary despite decades clinical trials targeting this stage disease, currently, no sepsis-specific therapies exist. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy emerged promising path forward. Highly investigated treatment strategies include cytokines growth factors, immune checkpoint inhibitors, even cellular therapies. There much be learned related illnesses, immunotherapy oncology, well recent COVID-19 pandemic, informed research. journey ahead long one, stratification according their status employment combination represent hopeful way

Language: Английский

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Coordinated inflammatory responses dictate Marburg virus control by reservoir bats

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 28, 2024

Bats are increasingly recognized as reservoirs of emerging zoonotic pathogens. Egyptian rousette bats (ERBs) the known reservoir Marburg virus (MARV), a filovirus that causes deadly disease (MVD) in humans. However, ERBs harbor MARV asymptomatically, likely due to coadapted and specific host immunity-pathogen relationship. Recently, we measured transcriptional responses MARV-infected ERB whole tissues, showing these possess tolerant strategy limits pro-inflammatory gene induction, presumably averting MVD-linked immunopathology. resistant by which actively limit burden remains elusive, hypothesize requires localized inflammatory unresolvable at bulk-tissue scale. Here, use dexamethasone attenuate assess replication, shedding disease. We show naturally mount coordinated liver foci infection, comprised recruited mononuclear phagocytes T cells, latter proliferate with MARV-specificity. When diminished, display heightened oral/rectal severe MVD-like pathology, demonstrating balance immunoprotective tolerance discreet MARV-resistant responses. These data further suggest natural immunomodulatory stressors like food scarcity habitat disruption may potentiate viral shedding, transmission therefore outbreak risk.

Language: Английский

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Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(2), P. 1059 - 1076

Published: Feb. 3, 2024

Language: Английский

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The Inflammatory Landscape of a Whole‐Tissue Explant Model of Hidradenitis Suppurativa

Experimental Dermatology, Journal Year: 2025, Volume and Issue: 34(2)

Published: Feb. 1, 2025

ABSTRACT Hidradenitis suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to the limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, many patients' medical needs not being met. This partly due historical scarcity ex vivo assays animal models that accurately recapitulate Thus, we have developed standardised whole‐tissue explant model HS examine its pathogenic mechanisms efficacy potential treatments within intact human tissue. We measured cytokine protein RNA whole tissue maintained in an agar‐media solution, finding IL‐6 IL‐8 concentrations trended upwards both explants healthy controls, while IL‐17A, IL‐1β, TNF‐α exhibited increases alone. also show were responsive with dexamethasone IL‐2. Not only do our results this effectively delivers throughout explants, but they elucidate which cytokines related process regardless state specifically, laying groundwork for future implementations model.

Language: Английский

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Nutritional management of individuals with obesity and COVID-19: ESPEN expert statements and practical guidance

Clinical Nutrition, Journal Year: 2021, Volume and Issue: 41(12), P. 2869 - 2886

Published: May 11, 2021

Language: Английский

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A critical analysis of SARS-CoV-2 (COVID-19) complexities, emerging variants, and therapeutic interventions and vaccination strategies

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 146, P. 112550 - 112550

Published: Dec. 15, 2021

Coronavirus is a family of viruses that can cause diseases such as the common cold, severe acute respiratory syndrome (SARS), and Middle East (MERS). The universal outbreak coronavirus disease 2019 (COVID-19) caused by SARS coronaviruses 2 (SARS-CoV-2) has become global pandemic. β-Coronaviruses, which SARS-CoV-2 (COVID-19), have spread in more than 213 countries, infected over 81 million people, 1.79 deaths. COVID-19 symptoms vary from mild fever, flu to pneumonia severely ill patients. Difficult breathing, distress (ARDS), kidney disease, liver damage, multi-organ failure ultimately lead death. Researchers are working on different pre-clinical clinical trials prevent this deadly pandemic developing new vaccines. Along with vaccines, therapeutic intervention an integral part healthcare response address ongoing threat posed COVID-19. Despite efforts understand fight against COVID-19, many challenges need be addressed. This article summarizes current pandemic, strains SARS-CoV-2, etiology, complexities, surviving medications so far, vaccination for treatment

Language: Английский

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Deuterated Drugs and Biomarkers in the COVID-19 Pandemic

ACS Omega, Journal Year: 2022, Volume and Issue: 7(46), P. 41840 - 41858

Published: Nov. 13, 2022

Coronavirus disease 2019 (COVID-19) is a highly contagious caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially identified in Wuhan (China) December 2019, COVID-19 rapidly spread globally, resulting pandemic. Carriers of SARS-CoV-2 can experience symptoms ranging from mild to (or no whatsoever). Although vaccination provides extra immunity toward SARS-CoV-2, there has been an urgent need develop treatments for alleviate carriers disease. In seeking potential treatment, deuterated compounds have played critical role either as therapeutic agents or internal MS standards studying pharmacological properties new drugs quantifying parent and metabolites. We >70 examples deuterium-labeled associated with treatment COVID-19. Of these, we found 9 repurposed >20 novel studied roles along total 38 (drugs, biomarkers, lipids) explored mass spectrometry standards. This review details synthetic pathways modes action these (if known), brief analysis each study.

Language: Английский

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The Role of Cyclodextrins in COVID-19 Therapy—A Literature Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2974 - 2974

Published: Feb. 3, 2023

Coronavirus disease-19 (COVID-19) emerged in December 2019 and quickly spread, giving rise to a pandemic crisis. Therefore, it triggered tireless efforts identify the mechanisms of disease, how prevent treat it, limit hamper its global dissemination. Considering above, search for prophylactic approaches has led revolution reglementary pharmaceutical pipeline, with approval vaccines against COVID-19 an unprecedented way. Moreover, drug repurposing scheme using regulatory-approved antiretroviral agents is also being pursued. However, their physicochemical characteristics or reported adverse events have sometimes limited use. Hence, nanotechnology been employed potentially overcome some these challenges, particularly cyclodextrins. Cyclodextrins are cyclic oligosaccharides that present hydrophobic cavities suitable complexing several drugs. This review, besides presenting studies on inclusion antiviral drugs cyclodextrins, aims summarize currently available therapeutic schemes COVID-19, highlighting those already make use cyclodextrins complexation. In addition, new underscored, potential application increase promising will be addressed. review describes instances which promotes increased bioavailability, action, solubility under analysis. The as active ingredient covered. Finally, toxicity regulatory issues well future perspectives regarding therapy provided.

Language: Английский

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Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells

Investigational New Drugs, Journal Year: 2023, Volume and Issue: 41(1), P. 142 - 152

Published: Jan. 25, 2023

The promising antitumor effects of progesterone derivatives have been identified in many studies. However, the specific mechanism action this class compounds has not fully described. Therefore, study, we investigated antiproliferative and (anti)estrogenic activities novel pentacyclic benzylidenes series. were evaluated on hormone-dependent MCF7 breast cancer cells using MTT test. Estrogen receptor α (ERα) activity was assessed by a luciferase-based reporter assay. Immunoblotting used to evaluate expression signaling proteins. All demonstrated inhibitory with IC50 values below 10 µM, whereas less active. These patterns may be associated lability geometry benzylidene molecules, which contributes an increase affinity interaction receptor. selected showed significant anti-estrogenic potency. Benzylidene 1d ((8 S,9 S,10R,13 S,14 S,17 S)-17-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one) most active assays. Apoptosis induced compound accompanied decreases CDK4, ERα, Cyclin D1 expression. Compounds 3d characterized high potency against resistant cells. leader confirmed PARP cleavage flow cytometry analysis. Compound caused cell arrest G2/M phase. Further analysis series is great importance for medicinal chemistry, drug design, oncology.

Language: Английский

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