Taras Shevchenko National University of Kyiv, Kyiv, 01601, Ukraine.
Institute of Molecular Biology and Genetics of NASU, Kyiv, 03143, Ukraine.
Sci Rep. 2021 Sep 7;11(1):17748. doi: 10.1038/s41598-021-97268-6.
Based on WHO reports the new SARS-CoV-2 coronavirus is currently widespread all over the world. So far > 162 million cases have been confirmed, including > 3 million deaths. Because of the pandemic still spreading across the globe the accomplishment of computational methods to find new potential mechanisms of virus inhibitions is necessary. According to the fact that C fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets, here the analysis of the potential binding mechanism between SARS-CoV-2 proteins 3CLpro and RdRp with C fullerene was done; it has resulted in one and two possible binding mechanisms, respectively. In the case of 3CLpro, C fullerene interacts in the catalytic binding pocket. And for RdRp in the first model C fullerene blocks RNA synthesis pore and in the second one it prevents binding with Nsp8 co-factor (without this complex formation, RdRp can't perform its initial functions). Then the molecular dynamics simulation confirmed the stability of created complexes. The obtained results might be a basis for other computational studies of 3CLPro and RdRp potential inhibition ways as well as the potential usage of C fullerene in the fight against COVID-19 disease.
基于世界卫生组织的报告，新型 SARS-CoV-2 冠状病毒目前在全球广泛传播。到目前为止，已经确诊了超过 1.62 亿例病例，包括超过 300 万人死亡。由于大流行仍在全球范围内蔓延，因此需要利用计算方法来寻找新的病毒抑制潜在机制。鉴于 C60 富勒烯（一种由碳组成的球形分子）已显示出对各种蛋白质靶标的抑制活性，我们在这里对 SARS-CoV-2 蛋白 3CLpro 和 RdRp 与 C60 富勒烯之间的潜在结合机制进行了分析；结果分别发现了一种和两种可能的结合机制。在 3CLpro 的情况下，C60 富勒烯与催化结合口袋相互作用。对于 RdRp，在第一个模型中，C60 富勒烯阻止 RNA 合成孔，在第二个模型中，它阻止与 Nsp8 辅助因子结合（如果没有这种复合物的形成，RdRp 就无法执行其初始功能）。然后，分子动力学模拟证实了所创建复合物的稳定性。这些结果可能为进一步研究 3CLPro 和 RdRp 的潜在抑制途径以及 C60 富勒烯在抗击 COVID-19 疾病方面的潜在用途提供依据。
