Establishment and application of a database for hepatitis C virus NS3/4A protease inhibitors and their drug resistance data
10.3969/j.issn.1001-5256.2018.09.012
- VernacularTitle:HCV NS3/4A蛋白酶抑制剂药物及其耐药信息数据库的建立和应用
- Author:
Lei XIE
1
;
Pei HAO
;
Ruihong WU
Author Information
1. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
- Publication Type:Research Article
- Keywords:
hepacivirus;
antiviral agents;
drug resistance;
databases as topic;
genotype
- From:
Journal of Clinical Hepatology
2018;34(9):1884-1890
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo establish a database for direct-acting antiviral agents (DAAs) targeting hepatitis C virus (HCV) NS3/4A protease and related resistance-associated variants, and to investigate its application in drug resistance analysis. MethodsThe published data and information of anti-NS3/4A DAAs and related drug resistance data were collected and mined. The in vitro data of viral drug-resistant mutations and resistance-associated variants identified in clinical treatment were entered into the database, and a statistical analysis was performed based on the type of drugs, HCV genotypes, positions of drug-resistant mutations, and type of substituted amino acids. Some of the results were available for online query on a website. Then the database was used to perform a multi-data analysis of the drug resistance of genotype 3 HCV, a well-known difficult-to-treat viral genotype. ResultsA database for anti-NS3/4A DAAs and their drug resistance data was established and some data were available for online query on a website (http://www.biosino.org/hcv/). This database consisted of the following four parts, with over ten thousands of pieces of information: the information of DAAs; the in vitro drug-resistance data of viral strains with different genotypes containing drug-resistant mutations; the prevalence of pre-existing resistance-associated variants and their detection rates in patients with treatment failure; the three-dimensional structures of the DAA-NS3/4A protease complex. This database was used to analyze drug resistance of all genotypes of HCV, and it was found that anti-NS3/4A DAAs had the poorest therapeutic effect in patients with genotype 3 HCV. Although the third-generation anti-NS3/4A DAAs had a good antiviral effect in patients with wild-type genotype 3 HCV, drug-resistant mutations might occur. ConclusionThis database is the first one in China for anti-NS3/4A DAAs and their drug-resistance data and provides an important resource of information and guidance for research on drug resistance and clinical treatment of HCV.
