Abstract：
Variants of SARS-CoV-2 pose significant challenges in public health due to their increased transmissibility and ability to evade natural immunity, vaccine protection, and monoclonal antibody therapeutics. The emergence of the highly transmissible Omicron variant and subsequent subvariants, characterized by an extensive array of over 32 mutations within the spike protein, intensifies concerns regarding vaccine evasion. In response, multiple antiviral therapeutics have received FDA emergency use approval, targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) regions, known to have relatively fewer mutations across novel variants. In this study, we evaluated the efficacy of nirmatrelvir (PF-07321332) and other clinically significant SARS-CoV-2 antivirals against a diverse panel of SARS-CoV-2 variants, encompassing the newly identified Omicron subvariants XBB1.5 and JN.1, using live-virus antiviral assays. Our findings demonstrate that while the last Omicron subvariants exhibited heightened pathogenicity in our animal model, nirmatrelvir and other clinically relevant antivirals consistently maintained their efficacy against all tested variants, including the XBB1.5 subvariant.
摘要：
SARS-CoV-2的变体由于其增加的传播性和逃避自然免疫的能力而对公共卫生构成重大挑战，疫苗保护,和单克隆抗体疗法。高度传播的Omicron变体和随后的亚变体的出现，特征在于刺突蛋白中超过32个突变的广泛阵列，加剧了对逃避疫苗的担忧。作为回应,多种抗病毒疗法已获得FDA紧急使用批准，靶向SARS-CoV-2RNA依赖性RNA聚合酶（RdRp）和主要蛋白酶（Mpro）区域，已知在新变体中突变相对较少。在这项研究中,我们评估了尼马特雷韦（PF-07321332）和其他具有临床意义的SARS-CoV-2抗病毒药物对多种SARS-CoV-2变体的疗效，包括新鉴定的Omicron亚变体XBB1.5和JN.1，使用活病毒抗病毒测定。我们的发现表明，虽然最后的Omicron亚变体在我们的动物模型中表现出更高的致病性，nirmatrelvir和其他临床相关的抗病毒药物始终保持其对所有测试变体的疗效，包括XBB1.5亚变体。
