Hepatitis B is a widespread and potentially life-threatening disease caused by the hepatitis B virus, tyrosine-methionine-aspartate-aspartate (YMDD) - motif mutant is a known HBV variant and responsible for the drug resistance during Long-term lamivudine treatment. In this work, spermine-coated silver nanoparticles were used as surface-enhanced Raman scattering enhancement matrices to detect mutations in single sites of the hepatitis B virus single-stranded DNA. The unique Raman finger-print spectrum of DNA based on spermine-coated silver nanoparticles was detected. And the signals from the phosphate backbone allowed to be an internal standard for standardize the surface-enhanced Raman spectrum of DNA oligonucleotides. The spectral changes were quantitatively related to the composition of adenine in the DNA strand, and the correlation performance reached 0.99. The relative standard deviation of surface-enhanced Raman spectroscopy signal corresponding to the tyrosine-isoleucine-aspartate-aspartate (YIDD), tyrosine-valine-aspartate-aspartate (YVDD), and YMDD was 5.43 %, 7.5 %, and 7.28 %, respectively. The proposed method provides a potential tool for YMDD-motif mutants detection and reference for therapeutic drug monitoring.

乙型肝炎是由乙型肝炎病毒，酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸（YMDD）引起的广泛且可能威胁生命的疾病-基序突变体是已知的HBV变异体，并在长期拉米夫定治疗期间引起耐药性。在这项工作中，将涂有精胺的银纳米颗粒用作表面增强的拉曼散射增强矩阵，以检测乙型肝炎病毒单链DNA单个位点的突变。检测了基于涂有精胺的银纳米颗粒的独特的DNA拉曼指纹图谱。来自磷酸盐主链的信号可以作为内标，用于标准化DNA寡核苷酸的表面增强拉曼光谱。光谱变化与DNA链中腺嘌呤的成分定量相关，相关性能达到0.99。分别对应于酪氨酸-异亮氨酸-天冬氨酸-天冬氨酸（YIDD），酪氨酸-缬氨酸-天冬氨酸-天冬氨酸（YVDD）和YMDD的表面增强拉曼光谱信号的相对标准偏差分别为5.43％，7.5％和7.28％ 。所提出的方法为YMDD-基序突变体的检测和治疗药物监测提供参考的潜在工具。