Introduction: Influenza is a severe respiratory viral infection that causes significant morbidity and mortality, due to annual epidemics and unpredictable pandemics. With the extensive use of neuraminidase inhibitor (NAI) drugs, the influenza B virus has carried different drug-resistant mutations. Thus, this study aimed to analyze the prevalence of drug-resistant mutations of the influenza B virus.

Methodology: Near full-length sequences of the neuraminidase (NA) region of all influenza B viruses from January 1, 2006, to December 31, 2018, were downloaded from public databases GISAID and NCBI. Multiple sequence alignments were performed using Clustal Omega 1.2.4 software. Subsequently, phylogenetic trees were constructed by FastTree 2.1.11 and clustered by ClusterPickergui_1.2.3.JAR. Then, the major drug resistance sites and surrounding auxiliary sites were analyzed by Mega-X and Weblogo tools.

Results: Among the amino acid sequences of NA from 2006 to 2018, only Clust04 in 2018 carried a D197N mutation of the NA active site, while other drug resistance sites were conserved without mutation. According to the Weblogo analysis, a large number of N198, S295, K373, and K375 mutations were found in the amino acid residues at the auxiliary sites surrounding D197, N294, and R374.

Conclusions: We found the D197N mutation in Clust04 of the 2018 influenza B virus, with a large number of N198, S295, K373, and K375 mutations in the helper sites around N197, N294, and R374 from 2006 to 2018. NA inhibitors are currently the only kind of specific antiviral agent for the influenza B virus, although these mutations cause mild NAIs resistance.