Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1080 - 1080

Published: Jan. 21, 2023

Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety wild Pu’er plants were two major ingredients responsible for the anti-influenza activity. As COVID-19 outbreak is still lurking, developing safe cost-effective therapeutics an urgent need. This study aimed to evaluate effects these compounds on infection mouse hepatitis virus (MHV), β-coronavirus serving as surrogate SARS-CoV. Treatment with (100 μM), but not theacrine, completely eliminated MHV infection, indicated by pronounced reduction in plaque formation, nucleocapsid protein expression, progeny production MHV. Subsequently, time-of-drug addition protocol, including pre-, co-, or post-treatment, was exploited further possible mechanism antiviral activity mediated strictinin, remdesivir, potential drug treatment SARS-CoV-2, used positive control against infection. The results showed that all three treatments remdesivir (20 μM) blocked In contrast, no significant effect observed when cells pre-treated prior while inhibition introduced upon viral adsorption (co-treatment) after entry (post-treatment). Of note, compared co-treatment group, inhibitory more striking post-treatment group. These indicate suppresses multiple mechanisms; it possibly interferes also critical step(s) Evidently, significantly inhibited might be suitable ingredient protection coronavirus

Language: Английский

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Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 167 - 178

Published: May 6, 2024

Language: Английский

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In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10802 - 10802

Published: Oct. 8, 2024

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as October 2024, continuous evolution variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections severe illnesses, contributing viral evolution. These cases increase risk new emerging. This study explores miniACE2 decoys novel strategy counteract variants. Using silico design molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity receptor-binding domain multiple than naturally soluble human ACE2. BPs expressed E. coli tested vitro, showing promising neutralizing effects. Notably, BP9 exhibited an average IC50 4.9 µg/mL across several variants, including Wuhan strain, Mu, Omicron BA.1, BA.2 low demonstrates potent ability BP9, indicating its efficacy at concentrations.Based on these findings, emerged therapeutic candidate combating evolving thereby positioning it potential emergency biopharmaceutical.

Language: Английский

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Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis

Drug Delivery, Journal Year: 2022, Volume and Issue: 29(1), P. 2846 - 2854

Published: Sept. 5, 2022

Favipiravir, an RNA-dependent RNA polymerase (RdRp) inhibitor, is used to treat patients infected with influenza virus and most recently SARS-CoV-2. However, poor accumulation of favipiravir in lung tissue following oral administration has required alternative method that directly targets the lungs. In this study, inhalation solution at a concentration 2 mg mL-1 was developed characterized for first time. The chemical stability inhaled two different media, phosphate buffer saline (PBS) normal (NS), investigated under conditions: 5 ± 3 °C, 25 °C/60% RH 5% RH, 40 °C/75% RH; addition constant light exposure. As result, PBS revealed superior over 12 months °C. Antiviral activity assessed concentrations between 0.25 real time cell analyzer on Vero-E6 were SARS-CoV-2/B.1.36. optimum found be mL-1, where minimum toxicity sufficient antiviral observed. Furthermore, viability assay against Calu-3 epithelial cells confirmed biocompatibility up 50 μM (7.855 mL-1). vitro aerodynamic profiles formulation, when delivered soft-mist inhaler indicated good targeting properties. These results suggest prepared could considered as suitable promising formulation pulmonary delivery treatment COVID-19.

Language: Английский

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Favipiravir, remdesivir, and lopinavir: metabolites, degradation products and their analytical methods

Drug Metabolism Reviews, Journal Year: 2024, Volume and Issue: 56(2), P. 127 - 144

Published: March 6, 2024

Severe acute respiratory syndrome 2 (SARS-CoV-2) caused the emergence of COVID-19 pandemic all over world. Several studies have suggested that antiviral drugs such as favipiravir (FAV), remdesivir (RDV), and lopinavir (LPV) may potentially prevent spread virus in host cells person-to-person transmission. Simultaneously with widespread use these drugs, their stability action mechanism also attracted attention many researchers. This review focuses on mechanism, metabolites degradation products (FAV, RDV LPV) demonstrates various methods for quantification discrimination different biological samples. Herein, instrumental analysis main form or metabolite are classified into two types: optical chromatography which last one combination detectors provides a powerful method routine analyses. Some representative reported this details them carefully explained. It is hoped will be good guideline study provide better understanding from aspects investigated study.

Language: Английский

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Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19

Journal of Antimicrobial Chemotherapy, Journal Year: 2024, Volume and Issue: 79(6), P. 1423 - 1431

Published: May 6, 2024

Abstract Background Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment disposition in lungs, via bronchoalveolar lavage, necessary to ensure levels at primary site SARS-CoV-2 infection are achieved. Objectives This Phase 1 study healthy subjects aimed assess bronchopulmonary pharmacokinetics, safety and tolerability repeated doses bemnifosbuvir. Methods A total 24 were assigned receive bemnifosbuvir twice daily 275, 550 or 825 mg up 3.5 days. Results AT-511, free base bemnifosbuvir, was largely eliminated from plasma within 6 h post dose all dosing groups. Antiviral consistently achieved lungs daily. The mean level nucleoside metabolite AT-273, surrogate active triphosphate drug, measured epithelial lining fluid 0.62 µM 4–5 dose. exceeded target vitro 90% effective concentration (EC90) 0.5 exposure against replication human airway cells. well tolerated across tested, most treatment-emergent adverse events reported mild severity resolved. Conclusions favourable pharmacokinetics profile demonstrates its potential as an COVID-19, currently under further clinical evaluation

Language: Английский

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Convalescent Plasma Therapy against COVID-19: An Update on the Changing Facets of the ongoing Pandemic

Current Pharmaceutical Biotechnology, Journal Year: 2023, Volume and Issue: 24(12), P. 1515 - 1523

Published: Feb. 3, 2023

The severe respiratory infections in the current pandemic coronavirus disease-19 (COVID-19) have influenced more or less every human life. first person to get infected with this virus was reported capital of Hubei province (Wuhan), China, late December 2019. Since disease has been declared a pandemic, research scholars and experts manufacturing new vaccines targeted therapies curb spread SARS-CoV-2. However, only limited options emerged so far, which yet require complete scientific validation by long-term data collection regarding safety efficacy. In wake recent emerging wave viz omicron variant, changing facets viral genome dearth preventative therapeutic possibilities for management COVID-19, usage Convalescent Plasma Therapy (CPT) may be looked at as potentially viable option treatment existing situation. Earlier, immune plasma used success H1N1 influenza virus, MERS-CoV, SARS-CoV-1 epidemics. present unpredictable situation created COVID-19 CPT is positive outcome amongst many individuals different parts world acceptable This article aimed an up-to-date evaluation literature on efficacy convalescent potential therapy, its effectiveness challenges treating COVID-19.

Language: Английский

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A Systematic Review of Clinical Pharmacokinetics of Inhaled Antiviral

Medicina, Journal Year: 2023, Volume and Issue: 59(4), P. 642 - 642

Published: March 23, 2023

Background and Objectives: The study of clinical pharmacokinetics inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy these drugs how best use them in treatment respiratory viral infections such influenza current COVID-19 pandemic. article presents a systematic review available pharmacokinetic data humans, which could be beneficial for clinicians adjusting doses diseased populations. Materials Methods: This followed Preferred Reporting Items Systematic Reviews Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, studies were screened by two independent reviewers assess their eligibility. Data extracted from eligible assessed quality appropriate tools. Results: evaluated parameters antiviral drugs. analyzed 17 studies, included Zanamivir, Laninamivir, Ribavirin with 901 participants, found that non-compartmental approach used most analysis. outcomes Cmax, AUC, t1/2 antivirals. Conclusions: Overall, well tolerated exhibited favorable profiles. provides valuable information on other infections.

Language: Английский

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Pre-Exposure Prophylaxis for viral infections other than HIV

Infezioni in Medicina, Journal Year: 2022, Volume and Issue: 30(3)

Published: Aug. 30, 2022

The battle against human viral infections has historically relied on two medical strategies, namely vaccines to protect from contagion and antivirals treat infected patients. In the absence of vaccines, have occasionally been used as peri-exposure prophylaxis, given either before (pre-exposure prophylaxis) or right after (post-exposure prophylaxis). an unprecedented way, use antiretrovirals chemoprophylaxis triumphed in HIV field. Indeed, oral daily at demand HIV-uninfected individuals engaged high-risk behaviors contagion. More recently, advent long-acting formulations allowed protection following intramuscular injections every three months. Can we envision a similar prophylactic strategy for other infections? such 'chemical vaccines' would fill unmet need when classical do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge immunity wanes. this review, discuss opportunities antiviral hepatitis B C, retroviruses HTLV-1 HIV-2, respiratory viruses influenza SARS-CoV-2, among others.

Language: Английский

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Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 8, 2024

ABSTRACT Bemnifosbuvir (BEM, AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of patients with COVID-19. Direct assessment disposition in lungs, via bronchoalveolar lavage, necessary to ensure levels at primary site SARS-CoV-2 infection are achieved. We conducted Phase 1 study healthy subjects assess bronchopulmonary pharmacokinetics, safety, and tolerability repeated doses BEM. A total 24 were assigned receive twice-daily (BID) BEM 275, 550, or 825 mg up 3.5 days. AT-511, free base BEM, was largely eliminated from plasma within 6 h post dose all dosing groups. Antiviral consistently achieved lungs 550 BID. The mean level nucleoside metabolite AT-273, surrogate active triphosphate drug, measured epithelial lining fluid 0.62 µM 4–5 dose. This exceeded target vitro 90% effective concentration (EC 90 ) 0.5 exposure against replication human airway cells. well tolerated across tested, most treatment-emergent adverse events reported mild severity resolved. favorable pharmacokinetics safety profile demonstrates its potential as an COVID-19, BID currently under further clinical evaluation

Language: Английский

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