Maslova A A, Matyugina E C, Shustova E Yu, Volok V P, Kozlovskaya L I, Kochetkov S N, Khandazhinskaya A L
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences, 108819 Moscow, Russia.
Mol Biol. 2022;56(3):469-473. doi: 10.1134/S0026893322030098. Epub 2022 Jun 3.
The development of specific drugs against SARS-CoV-2 infection is a major challenge facing global science and healthcare. Despite numerous attempts, there are still no truly effective drugs. Currently, the main approach in the creation of drugs against COVID-19 is repurposing, i.e., re-profiling existing drugs approved for medical use, for example, the use of a drug for the treatment of Ebola-Remdesivir, and the use of a drug for the treatment of influenza-Favipiravir. However, it is already obvious that these drugs are not specific enough nor effective enough. Another promising approach is the creation of new molecules, but it should be noted immediately that implementation requires much more time and costs. However, the search for new SARS-CoV-2 specific antiviral agents continues. The aim of our work was the creation of new 5-substituted uridine derivatives as potential inhibitors of coronavirus RNA-dependent RNA polymerase. The substances were obtained in high yields by the Suzuki‒Miyaura reaction and characterized using modern physicochemical methods. However, testing of their antiviral activity against SARS-CoV-2 did not reveal a significant inhibitory effect.
研发针对新型冠状病毒2019感染的特效药物是全球科学界和医疗界面临的一项重大挑战。尽管进行了无数次尝试，但仍没有真正有效的药物。目前，研发抗新冠病毒药物的主要方法是药物再利用，即重新评估已获医疗批准的现有药物的用途，例如，将治疗埃博拉的药物瑞德西韦，以及治疗流感的药物法匹拉韦用于治疗新冠病毒。然而，很明显这些药物的特异性和有效性都不够。另一种有前景的方法是合成新分子，但需要立即指出的是，这需要更多的时间和成本。然而，针对新型冠状病毒2019的新型特异性抗病毒药物的研发仍在继续。我们工作的目标是合成新的5-取代尿苷衍生物，作为冠状病毒RNA依赖性RNA聚合酶的潜在抑制剂。这些物质通过铃木-宫浦反应高产率获得，并使用现代物理化学方法进行了表征。然而，对它们针对新型冠状病毒2019的抗病毒活性测试并未显示出显著的抑制作用。
