Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking
In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papain-like protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through several mechanisms. The efficiency of inhibitors was evaluated based on docking scores using AutoDock Vina software. Strong ligand –protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and...
Source: Network Modeling Analysis in Health Informatics and Bioinformatics - February 4, 2022 Category: Bioinformatics Source Type: research
Viruses, Vol. 13, Pages 2489: Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections
Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections. (Source: Viruses)
Source: Viruses - December 11, 2021 Category: Virology Authors: Aleksandr Ianevski Rouan Yao Eva Zusinaite Laura Sandra Lello Sainan Wang Eunji Jo Jaewon Yang Erlend Ravlo Wei Wang Hilde Lysvand Kirsti L øseth Valentyn Oksenych Tanel Tenson Marc P. Windisch Minna M. Poranen Anni I. Nieminen Svein Arne Nordb ø Mona H Tags: Article Source Type: research
Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus
Eur J Med Chem. 2021 Dec 1;228:114033. doi: 10.1016/j.ejmech.2021.114033. Online ahead of print.ABSTRACTA series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC50 values almost equivalent to the clinical drug telaprevir (EC50 = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in ...
Source: European Journal of Medicinal Chemistry - December 9, 2021 Category: Chemistry Authors: Yonghua Liu Jianrui Li Yuxi Gu Ling Ma Shan Cen Zonggen Peng Laixing Hu Source Type: research
Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus
Eur J Med Chem. 2021 Dec 1;228:114033. doi: 10.1016/j.ejmech.2021.114033. Online ahead of print.ABSTRACTA series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC50 values almost equivalent to the clinical drug telaprevir (EC50 = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in ...
Source: European Journal of Medicinal Chemistry - December 9, 2021 Category: Chemistry Authors: Yonghua Liu Jianrui Li Yuxi Gu Ling Ma Shan Cen Zonggen Peng Laixing Hu Source Type: research
Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus
Eur J Med Chem. 2021 Dec 1;228:114033. doi: 10.1016/j.ejmech.2021.114033. Online ahead of print.ABSTRACTA series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC50 values almost equivalent to the clinical drug telaprevir (EC50 = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in ...
Source: European Journal of Medicinal Chemistry - December 9, 2021 Category: Chemistry Authors: Yonghua Liu Jianrui Li Yuxi Gu Ling Ma Shan Cen Zonggen Peng Laixing Hu Source Type: research
Pre-Steady-State Kinetics of the SARS-CoV-2 Main Protease as a Powerful Tool for Antiviral Drug Discovery
We examined the kinetic mechanism of peptide substrate binding and cleavage by wild-type Mpro and by its catalytically inactive mutant C145A. The enzyme induces conformational changes of the peptide during the reaction. The inhibition of Mpro by boceprevir, telaprevir, GC-376, PF-00835231, or thimerosal was investigated. Detailed pre–steady-state kinetics of the interaction of the wild-type enzyme with the most potent inhibitor, PF-00835231, revealed a two-step binding mechanism, followed by covalent complex formation. The C145A Mpro mutant interacts with PF-00835231 approximately 100-fold less effectively. Nevertheless,...
Source: Frontiers in Pharmacology - December 6, 2021 Category: Drugs & Pharmacology Source Type: research
Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
AbstractThis work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the dire...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 19, 2021 Category: Drugs & Pharmacology Authors: Xavier Woot de Trixhe,
Wojciech Krzyzanski,
An Vermeulen,
Juan Jos é Perez‐Ruixo Tags: ARTICLE Source Type: research
Amino acid and peptide-based antiviral agents
ChemMedChem. 2021 Jul 13. doi: 10.1002/cmdc.202100397. Online ahead of print.ABSTRACTAn important number of antiviral agents used in clinical practice are amino acids, short peptides, or peptidomimetics. Among them, several HIV protease inhibitors (e.g. saquinavir, indinavir), HCV protease inhibitors (e.g. boceprevir, telaprevir), and HCV NS5A protein inhibitors contributed to a signicant reduction of mortality due to AIDS and hepatitis. However, there exists a constant need for the discover of new antiviral agents and the development of existing ones, and amino acids both proteinogenic and non-proteinogenic nature serve a...
Source: ChemMedChem - July 13, 2021 Category: Chemistry Authors: Andrzej Stanis ław Skwarecki Micha ł Grzegorz Nowak Maria Jolanta Milewska Source Type: research
Amino acid and peptide-based antiviral agents
ChemMedChem. 2021 Jul 13. doi: 10.1002/cmdc.202100397. Online ahead of print.ABSTRACTAn important number of antiviral agents used in clinical practice are amino acids, short peptides, or peptidomimetics. Among them, several HIV protease inhibitors (e.g. saquinavir, indinavir), HCV protease inhibitors (e.g. boceprevir, telaprevir), and HCV NS5A protein inhibitors contributed to a signicant reduction of mortality due to AIDS and hepatitis. However, there exists a constant need for the discover of new antiviral agents and the development of existing ones, and amino acids both proteinogenic and non-proteinogenic nature serve a...
Source: ChemMedChem - July 13, 2021 Category: Chemistry Authors: Andrzej Stanis ław Skwarecki Micha ł Grzegorz Nowak Maria Jolanta Milewska Source Type: research
Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 < em > in Vitro < /em >
This study could inform development and application of protease inhibitors for optimized antiviral treatments of COVID-19.PMID:34097489 | DOI:10.1128/AAC.02680-20 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - June 7, 2021 Category: Microbiology Authors: Karen A Gammeltoft Yuyong Zhou Carlos R Duarte Hernandez Andrea Galli Anna Offersgaard Rui Costa Long V Pham Ulrik Fahn øe Shan Feng Troels K H Scheel Santseharay Ramirez Jens Bukh Judith M Gottwein Source Type: research
Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 < em > in Vitro < /em >
This study could inform development and application of protease inhibitors for optimized antiviral treatments of COVID-19.PMID:34097489 | DOI:10.1128/AAC.02680-20 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - June 7, 2021 Category: Microbiology Authors: Karen A Gammeltoft Yuyong Zhou Carlos R Duarte Hernandez Andrea Galli Anna Offersgaard Rui Costa Long V Pham Ulrik Fahn øe Shan Feng Troels K H Scheel Santseharay Ramirez Jens Bukh Judith M Gottwein Source Type: research
Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 < em > in Vitro < /em >
This study could inform development and application of protease inhibitors for optimized antiviral treatments of COVID-19.PMID:34097489 | DOI:10.1128/AAC.02680-20 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - June 7, 2021 Category: Microbiology Authors: Karen A Gammeltoft Yuyong Zhou Carlos R Duarte Hernandez Andrea Galli Anna Offersgaard Rui Costa Long V Pham Ulrik Fahn øe Shan Feng Troels K H Scheel Santseharay Ramirez Jens Bukh Judith M Gottwein Source Type: research
