The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major antigen stimulating the host’s protective immune response. Here we assessed the efficacy of therapeutic monoclonal antibodies (mAbs) against Omicron variant (B.1.1.529) sublineage BA.1 variants in Syrian hamsters. Of the FDA-approved therapeutic mAbs tested (that is, REGN10987/REGN10933, COV2-2196/COV2-2130 and S309), only COV2-2196/COV2-2130 efficiently inhibited BA.1 replication in the lungs of hamsters, and this effect was diminished against a BA.1.1 variant possessing the S-R346K substitution. In addition, treatment of BA.1-infected hamsters with molnupiravir (a SARS-CoV-2 RNA-dependent RNA polymerase inhibitor) or S-217622 (a SARS-CoV-2 protease inhibitor) strongly reduced virus replication in the lungs. These findings suggest that the use of therapeutic mAbs in Omicron-infected patients should be carefully considered due to mutations that affect efficacy, and demonstrate that the antiviral compounds molnupiravir and S-217622 are effective against Omicron BA.1 variants.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的刺突蛋白是刺激宿主保护性免疫反应的主要抗原。在这里，我们评估了治疗性单克隆抗体 (mAb) 针对叙利亚仓鼠中 Omicron 变体 (B.1.1.529) 亚系 BA.1 变体的功效。在测试的 FDA 批准的治疗性 mAb（即 REGN10987/REGN10933、COV2-2196/COV2-2130 和 S309）中，只有 COV2-2196/COV2-2130 有效抑制 BA.1 在仓鼠肺部的复制，并且这种作用对具有 S-R346K 替代的 BA.1.1 变体减少。此外，用莫努匹拉韦（一种 SARS-CoV-2 RNA 依赖性 RNA 聚合酶抑制剂）或 S-217622（一种 SARS-CoV-2 蛋白酶抑制剂）治疗 BA.1 感染的仓鼠可大大减少病毒在肺部的复制。