Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations

We investigated the mutation profiles of severe acute respiratory syndrome coronavirus 2 in samples collected from a molnupiravir and nirmatrelvir/ritonavir combination therapy in macaques. We found that molnupiravir induced several nirmatrelvir resistance mutations at low abundance that were not further selected in combination therapy. Coadministration of nirmatrelvir/ritonavir lowered the magnitude of the mutagenetic effect of molnupiravir.

本研究针对猕猴接受莫努匹拉韦(molnupiravir)与奈玛特韦/利托那韦(nirmatrelvir/ritonavir)联合治疗后采集的样本，开展了严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2）的突变谱分析。研究发现，莫努匹拉韦可诱导出若干低丰度的奈玛特韦耐药突变，但此类突变未在联合治疗方案中得到进一步筛选富集。联合给予奈玛特韦/利托那韦可削弱莫努匹拉韦的诱变效应强度。