Establishment and application of a database for hepatitis C virus NS3/4A protease inhibitors and their drug resistance data

Objective To establish a database for direct-acting antiviral agents (DAAs) targeting hepatitis C virus (HCV) NS3/4 A protease and related resistance-associated variants, and to investigate its application in drug resistance analysis. Methods The published data and information of anti-NS3/4 A 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. Results A database for anti-NS3/4 A 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-NS3/4 A protease complex.This database was used to analyze drug resistance of all genotypes of HCV, and it was found that anti-NS3/4 A DAAs had the poorest therapeutic effect in patients with genotype 3 HCV. Although the third-generation anti-NS3/4 A DAAs had a good antiviral effect in patients with wild-type genotype 3 HCV, drug-resistant mutations might occur. Conclusion This database is the first one in China for anti-NS3/4 A 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.