Approaches for the Development of Antiviral Compounds: The Case of Hepatitis C Virus

Schinazi, Raymond F.; Coats, Steven J.; Bassit, Leda; Lennerstrand, Johan; Nettles, James H.; Hurwitz, Selwyn J.

doi:10.1007/978-3-540-79086-0_2

Cited by 9 publications

(9 citation statements)

References 107 publications

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“…Recently discovered thienoimidazole derivatives (24) [48] were found to be active against NS5A of HCV EC 50 ¼ 17, 8 nM (GT-1a, GT-1b respectively), hydroxamino-a-pyranone carboxamides (25) also exhibited activity against HCV with EC 50 ¼ 0.18 mM [49]. The pyrimidine based sulfonamide (26) analogues were also tested for The benzidine prolinamide derivatives exerted anti-HCV properties against genotypes 2a and 1b demonstrated its potency towards genotype 1b (EC 50 ¼ 0.028 nM).…”

Section: Nucleoside Non-nucleoside and Protease Inhibitors As Anti-hmentioning

confidence: 99%

A review on HCV inhibitors: Significance of non-structural polyproteins

Ganta¹,

Gedda

Rathnakar

et al. 2019

European Journal of Medicinal Chemistry

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a b s t r a c tHepatitis C virus (HCV) mortality and morbidity is a world health misery with an approximate 130e150 million chronically HCV tainted and suffering individuals and it initiate critical liver malfunction like cirrhosis, hepatocellular carcinoma or liver HCV cancer. HCV NS5B protein one of the best studied therapeutic target for the identification of new drug candidates to be added to the combination or multiple combination medication recently approved. During the past few years, NS5B has thus been an important object of attractive medicinal chemistry endeavors, which induced to the surfacing of betrothal preclinical drug molecules. In this scenario, the current review set limit to discuss research published on NS5B and few other therapeutic functional inhibitors concentrating on hit investigation, hit to lead optimization, ADME parameters evaluation, and the SAR data which was out for each compound type and similarity taken into consideration. The discussion outlined in this specific review will surly helpful and vital tool for those medicinal chemists investigators working with HCV research programs mainly pointing on NS5B and set broad spectrum identification of creative anti HCV compounds. This mini review also tells each and every individual compound ability related how much they are active against NS5B and few other targets.

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Section: Nucleoside Non-nucleoside and Protease Inhibitors As Anti-hmentioning

confidence: 99%

A review on HCV inhibitors: Significance of non-structural polyproteins

Ganta¹,

Gedda

Rathnakar

et al. 2019

European Journal of Medicinal Chemistry

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“…Ribavirin and IFN‐α, although often poorly tolerated, remain the cornerstone for the treatment of HCV infection [1,2]. Novel nucleoside analogues under clinical investigation provide hope for significant reduction in viral loads and demonstrate results that mirror the marked reduction in systemic virus reported for protease inhibitor treatment of HIV‐1 infected individuals [105,107,108]. In addition, this class of drug appears to be genotype independent making them highly valuable for combination modalities.…”

Section: Novel Hcv Inhibitors: Recent Progress and Future Designmentioning

confidence: 99%

HCV drug discovery aimed at viral eradication

Schinazi

Bassit

Gavegnano

2010

Journal of Viral Hepatitis

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SUMMARY Hepatitis C virus (HCV) causes significant morbidity and mortality worldwide with nearly 3% of the world population infected by this virus. Fortunately, this virus does not establish latency, and hence it may be possible to eradicate it. HCV is strongly associated with liver cirrhosis and hepatocellular carcinoma and is currently treated with pegylated interferon-α (peg-IFN-α) and ribavirin. Unfortunately, these limited treatment options often produce significant side effects, and currently, complete eradication of virus with combined drug modalities has not yet been achieved for the majority of chronically HCV-infected individuals. Restricted treatment options, lack of a universal cure for HCV and the link between chronic infection, liver cirrhosis and hepatocellular carcinoma necessitate design of novel drugs and treatment options. Understanding the relationship between the immune response, viral clearance and inhibition of viral replication with pharmacology-based design can ultimately allow for complete eradication of HCV. This review focuses upon significant novel preclinical and clinical specifically targeted antiviral therapy (STAT-C) drugs under development, highlights their mechanism of action, and discusses their impact on systemic viral loads and permanent clearance of infection.

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“…The use of in vitro settings to investigate and identify new compounds has made important advances over the past 100 years, particularly regarding the development of antivirals (Prusoff et al, 1989;Schinazi et al, 2009). More recently, new studies have relied on the ability to establish qualitative or semi-quantitative relations between molecular structures to test these hypotheses (Li, 2001).…”

Section: Discussionmentioning

confidence: 99%

Molecular dynamics suggests antiviral compounds active against Dengue Virus show similar binding patterns to Zika Virus proteins

Neto

Soares

Pour

et al. 2018

Preprint

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The Zika virus (ZIKV) arrival in Brazilian territory brought to light the need for preparedness regarding arboviruses in Brazil. Compound screening is a cumbersome process dependent upon in vitro testing and validation. Recently, virtual screening methods have improved precision and reliability providing a framework for in silico testing of lead compound candidates. Here we have applied these methods on compounds that were previously shown to be active against Dengue virus in vitro, taking the structural information of such compounds and applying docking methods to identify putative binding sites. A molecular dynamics approach was also used to refine the docking results. The computational experiments ran here suggests that compounds such as Epigallocatechin Gallate, Ergotamine and Avermectin-B1a bind to active sites on the viral enzymes NS5 and NS3, as well as on its Envelope protein. Refinement shows that such bindings were not lost during the production run and key regions on both enzymes were structurally displaced on average over the simulation time. Interestingly there is no documented drug interactions among these candidates, raising the possibility of drug combinations during treatments.Moreover, the candidate compounds have been extensively studied, thus providing important information regarding intracellular interactions caused by them, which are also associated with pathways exploited by the virus, suggesting possible side interactions hindering the replication process.

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Approaches for the Development of Antiviral Compounds: The Case of Hepatitis C Virus

Cited by 9 publications

References 107 publications

A review on HCV inhibitors: Significance of non-structural polyproteins

A review on HCV inhibitors: Significance of non-structural polyproteins

HCV drug discovery aimed at viral eradication

Molecular dynamics suggests antiviral compounds active against Dengue Virus show similar binding patterns to Zika Virus proteins

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