SARS-CoV-2 Sequencing

Successful antiviral drugs, in theory, exert their virus-specific effects by interacting with viral receptors, virally encoded enzymes, viral structural components, viral genes, or their transcripts without disturbing cellular metabolism or function. Although nirmatrelvir has been used for the treatment of SARS-CoV-2/COVID-19, some reports have been mentioned the emergence of drug-resistant-related amino acid substitutions. For elucidation of the mechanism of development of resistance to MPI such as NIR by SARS-CoV-2, it is critical to acquire MPI-resistant SARS-CoV-2 variant(s), which should be of high utility in further designing more efficacious and resistance-deferring anti-SARS-CoV-2 drugs.

理论上，疗效确切的抗病毒药物可通过与病毒受体、病毒编码酶、病毒结构组分、病毒基因及其转录本相结合，发挥病毒特异性的抗病毒效应，且不会干扰细胞的正常代谢与功能。奈玛特韦（nirmatrelvir）已被用于治疗严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引发的新型冠状病毒肺炎（COVID-19），但已有多项研究报道了与耐药相关的氨基酸替换事件。为阐明SARS-CoV-2对主蛋白酶抑制剂（MPI）（如NIR）产生耐药性的作用机制，获取耐MPI的SARS-CoV-2变异株至关重要，此类变异株可为后续研发更高效、更能延缓耐药性产生的抗SARS-CoV-2药物提供极高的应用价值。