Hepatitis C NS3 Protease: Restoration of NS4A Cofactor Activity by N-Biotinylation of Mutated NS4A Using Synthetic Peptides

Butkiewicz, Nancy; Yao, Nanhua; Wright-Minogue, Jacquelyn; Zhang, Rumin; Ramanathan, Lata; Lau, Johnson Y. N.; Hong, Zhi; Dasmahapatra, Bimal

doi:10.1006/bbrc.1999.1898

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…The NS4A protein is a short polypeptide of 54 amino acids and the cofactor of the NS3 serine protease. It places NS3 protease on intracellular membranes through the N-terminal transmembrane segment in its structure, contributes to its correct folding by joining the N-terminal protease region, stabilizes protease against proteolytic degradation, and activates protease activity [30].…”

Section: Protein Ns4amentioning

confidence: 99%

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Hepatitis C Virus Structure and Diagnostic Methods

Deniz¹,

Akhan²

2023

Hepatitis C - Recent Advances

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In recent years, with the use of direct-acting antivirals (DAA) in the treatment of chronic hepatitis C (CHC), the success rate has exceeded 90%. The implementation of these strong therapies has reduced the role of monitoring therapy with HCV RNA tests. The aim of this study is to compare the HCV core antigen test with HCV RNA in terms of correlation, effectiveness and cost in patients who started DAA and to evaluate the usability of HCV Ag as a routine laboratory test.This study includes 76 patients with CHC. Patients with positive HCV RNA, over 18 years old and who will initiate DAA are included. HCV Ag level was studied in all samples by using ARCHITECT core antigen measurement Abbott method. HCV RNA and anti-HCV levels compared with HCV Ag levels. When compared before and after treatment, HCV RNA level, HCV Ag level were found to be significantly different (p <0.001). Before treatment, HCV RNA and HCV Ag levels were found to be positive correlations (correlation coefficient:0,419). It has been demonstrated in the our study that HCV Ag measurement is a very successful and cost effective in detecting viremic patients and evaluating virological response, which are the two most important factors in the management of CHC.

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Section: Protein Ns4amentioning

confidence: 99%

“…Approximately 185 million people worldwide are infected with HCV. The global prevalence of infection is known as 2-3% [30,48]. The most affected regions are Eastern Mediterranean and European regions, with a prevalence of 2.3 and 1.5%, respectively.…”

Section: Epidemiology Of Hepatitis C Virusmentioning

confidence: 99%

Hepatitis C Virus Structure and Diagnostic Methods

Deniz¹,

Akhan²

2023

Hepatitis C - Recent Advances

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Section: Therapeutic Approaches – Ns3 Protease Inhibition As a Responmentioning

confidence: 99%

“…Recently, it has been proposed that the Φx 3 Φ motif is the common structural element involved in cofactor binding to the protease [108]. This motif consists of two bulky hydrophobic residues separated by three unspecified residues; it has been speculated that additional residues, located outside this sequence motif, would contribute to the stringent specificity of the protease for the corresponding polyprotein substrate [108]. A mutagenesis study with the DENv NS2B cofactor has revealed that substitution of the Φ residues (corresponding to residues Leu75 and Ile79) with alanine results in a decrease of the NS2B–NS3pro autoprocessing to approximately 55 and 75% of the wild‐type value [109].…”

Section: Therapeutic Approaches – Ns3 Protease Inhibition As a Responmentioning

confidence: 99%

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Progress for dengue virus diseases

Melino

Paci

2007

The FEBS Journal

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Transmitted by the Aedes aegypti mosquito, the dengue virus is the etiological agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, and, as such, is a significant factor in the high death rate found in most tropical and subtropical areas of the world. Dengue diseases are not only a health burden to developing countries, but pose an emerging problem worldwide. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators during dengue disease plays a key role in inducing plasma leakage, shock and hemorrhagic manifestations. Currently, there are no vaccines available against dengue virus, although several tetravalent live‐attenuated dengue vaccines are in clinical phases I or II, and prevention through vaccination has become a major priority on the agendas of the World Health Organization and of national ministries of health and military organizations. An alternative to vaccines is found in therapeutic‐based approaches. Understanding the molecular mechanisms of viral replication has led to the development of potential drugs, and new molecular viral targets for therapy are emerging. The NS3 protease domain of the NS3 protein is responsible for processing the viral polyprotein and its inhibition is one of the principal aims of pharmacological therapy. This review is an overview of the progress made against dengue virus; in particular, it examines the unique properties – structural and functional – of the NS3 protease for the treatment of dengue virus infections by the inhibition of viral polyprotein processing.

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5 Inhibitors of Hepatitis C Virus NS3•4A Protease: An Overdue Line of Therapy

Perni¹,

Kwong²

2002

Progress in Medicinal Chemistry

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Hepatitis C NS3 Protease: Restoration of NS4A Cofactor Activity by N-Biotinylation of Mutated NS4A Using Synthetic Peptides

Cited by 6 publications

References 21 publications

Hepatitis C Virus Structure and Diagnostic Methods

Hepatitis C Virus Structure and Diagnostic Methods

Progress for dengue virus diseases

5 Inhibitors of Hepatitis C Virus NS3•4A Protease: An Overdue Line of Therapy

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