Lopez Uxua Modrego, Hasan Md Mehedi, Havranek Brandon, Islam Shahidul M
Department of Chemistry, Delaware State University, Dover, DE 19901, USA.
Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, USA.
Curr Clin Microbiol Rep. 2024 Sep;11(3):127-139. doi: 10.1007/s40588-024-00229-6. Epub 2024 Jun 24.
SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.
Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.
This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.
与许多其他病毒一样，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）会发生基因突变。一些突变导致新的关注变异株（VOC）出现，影响传播性、疾病严重程度和抗病毒药物的有效性。持续监测和研究对于理解变异株行为以及制定有效的应对策略至关重要，包括识别可能影响当前药物治疗的突变。
奈玛特韦和恩昔洛韦等抗病毒疗法专注于抑制3CL蛋白酶，而瑞德西韦、法匹拉韦和莫努匹拉韦则靶向nsp12，从而降低病毒载量。然而，3CL蛋白酶和nsp12中耐药突变的出现可能会影响这些小分子药物治疗的效果。
本手稿总结了3CL蛋白酶和nsp12中的突变，这些突变可能会降低药物疗效。此外，它还概括了针对SARS-CoV-2病毒蛋白的小分子抗病毒药物的最新进展，包括它们对新出现变异株产生耐药性的可能性。
