Quantifying the Evolutionary Constraints and Potential of Hepatitis C Virus NS5A Protein.

ABSTRACT: RNA viruses, such as hepatitis C virus (HCV), influenza virus, and SARS-CoV-2, are notorious for their ability to evolve rapidly under selection in novel environments. It is known that the high mutation rate of RNA viruses can generate huge genetic diversity to facilitate viral adaptation. However, less attention has been paid to the underlying fitness landscape that represents the selection forces on viral genomes, especially under different selection conditions. Here, we systematically quantified the distribution of fitness effects of about 1,600 single amino acid substitutions in the drug-targeted region of NS5A protein of HCV. We found that the majority of nonsynonymous substitutions incur large fitness costs, suggesting that NS5A protein is highly optimized. The replication fitness of

SUBMITTER: Dai L 

PROVIDER: S-EPMC8546995 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature