Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan.
Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan; Department of Science System Simulation, Pukyong National University, Busan, Republic of Korea.
Antiviral Res. 2022 Sep;205:105372. doi: 10.1016/j.antiviral.2022.105372. Epub 2022 Jul 4.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence's impact on choosing optimal drug treatment.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)奥密克戎亚变体 BA.2 已在许多国家传播,取代了早期的奥密克戎亚变体 BA.1 和其他变体。在这里,我们使用细胞培养感染测定法,定量比较了 BA.2 和 BA.1 与其他关注变体(阿尔法、伽马和德尔塔)对五种批准的中和抗体和抗病毒药物的固有敏感性。我们的测定法揭示了这些变体对抗体的不同敏感性,包括 BA.1 和 BA.2 对 casirivimab 和 BA.1 对 imdevimab 的反应丧失。相比之下,EIDD-1931 和 nirmatrelvir 对这些变体表现出更保守的活性。病毒反应谱结合数学分析估计了在临床浓度下变体之间抗病毒效果的差异。这些分析提供了重要的证据,深入了解了变体出现对选择最佳药物治疗的影响。