Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs

Saleem, Ammara; Akhtar, Muhammad Furqan; Mushtaq, Muhammed Fahd; Saleem, Muhammad; Muhammad, Syed Taqi; Akhtar, Bushra; Sharif, Ali; Peerzada, Sohaib

doi:10.17179/excli2016-582

Cited by 2 publications

(2 citation statements)

References 72 publications

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“…The peroral bioavailability of 13b-K was also evaluated. Inspired by the fact that liposomes have already been used in the context of novel antivirals, we used a 1,2,-dioleoyl-sn-glycero-3-phospho- l -serine (DOPS)-based large unilamellar vesicle (LUV) formulation to dissolve 13b-K at higher concentrations. Moreover, LUV facilitate absorption as they fuse more easily with membranes and, thereby, enhance peroral bioavailability, especially in the case of peptidomimetic molecules like 13b-K , as the gastrointestinal epithelium frequently represents not only a physical but also a biochemical barrier for proteins and peptides. − We administered the 13b-K LUV formulation at 100 mg/kg perorally and determined plasma and urine concentrations at designated time points.…”

Section: Resultsmentioning

confidence: 99%

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Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease

Cooper¹,

Zhang

Ibrahim

et al. 2022

J. Med. Chem.

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SARS-CoV-2 is the causative agent behind the COVID-19 pandemic. The main protease (Mpro, 3CLpro) of SARS-CoV-2 is a key enzyme that processes polyproteins translated from the viral RNA. Mpro is therefore an attractive target for the design of inhibitors that block viral replication. We report the diastereomeric resolution of the previously designed SARS-CoV-2 Mpro α-ketoamide inhibitor 13b. The pure (S,S,S)-diastereomer, 13b-K, displays an IC50 of 120 nM against the Mpro and EC50 values of 0.8–3.4 μM for antiviral activity in different cell types. Crystal structures have been elucidated for the Mpro complexes with each of the major diastereomers, the active (S,S,S)-13b (13b-K), and the nearly inactive (R,S,S)-13b (13b-H); results for the latter reveal a novel binding mode. Pharmacokinetic studies show good levels of 13b-K after inhalative as well as after peroral administration. The active inhibitor (13b-K) is a promising candidate for further development as an antiviral treatment for COVID-19.

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Section: Resultsmentioning

confidence: 99%

“…Recrystallization from acetonitrile afforded the title compound as an off-white solid. 1 24 = +86.2°(c = 0.5, MeOH); >98% purity determined by SFC (Trefoil AMY1 (150 × 3.0 nm, 2.5 μm), IPA:CO 2 (34.5% IPA isocratic)). (13).…”

Section: Methyl (S)-2-(2-(3-((tert-butoxycarbonyl)amino)-2-oxopyridin...mentioning

confidence: 99%

Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease

Cooper¹,

Zhang

Ibrahim

et al. 2022

J. Med. Chem.

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Highlight report: General determinants of steatosis

Albrecht

2018

EXCLI Journal; 17:Doc1194; ISSN 1611-2156

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Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs

Cited by 2 publications

References 72 publications

Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease

Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease

Highlight report: General determinants of steatosis

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