Fundação Oswaldo Cruz/Fiocruz, Unidade Rondônia, Laboratório de Bioinformática e Química Medicinal, Rua da Beira, 7671, 76812-245 Porto Velho, RO, Brazil.
Programa de Pós-Graduação em Biologia Experimental, Fundação Universidade Federal de Rondônia (UNIR), Av. Pres. Dutra, 2965, 76801-058 Porto Velho, RO, Brazil.
An Acad Bras Cienc. 2024 May 10;96(2):e20231336. doi: 10.1590/0001-3765202420231336. eCollection 2024.
The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.
疾病冠状病毒 COVID-19 已在全球范围内导致数百万人死亡。在 SARS-CoV-2 的蛋白质中,非结构蛋白 12(NSP12)在 COVID 感染期间起着关键作用,是 RNA 依赖性 RNA 聚合酶复合物的一部分。监测 NSP12 多态性对于设计新的抗病毒药物和监测病毒进化非常重要。本研究分析了 2020 年至 2022 年期间在巴西亚马逊州玛瑙斯市人群中循环 SARS-CoV-2 中检测到的 NSP12 突变。发现最常见的突变是 P323L 和 G671S。文献中的报道表明,这些突变与传染性效率有关,这可能导致该地区的病例数量极高。此外,这里描述的两个突变(E796D 和 R914K)彼此接近,并且 RMSD 与文献中描述的对 NSP12 酶性能有影响的突变 M794V 和 N911K 相似。这些数据表明需要监测 NSP12 中新型突变的出现,以便更好地了解它们对当前使用的治疗方法和新药物设计的影响。