FSBSI "Chumakov FSC R&D IBP RAS", Moscow, 108819, Russia; Institute of Translational Medicine and Biotechnology, Sechenov Moscow State Medical University, Moscow, 119991, Russia.
FSBSI "Chumakov FSC R&D IBP RAS", Moscow, 108819, Russia.
Eur J Med Chem. 2021 Aug 5;220:113467. doi: 10.1016/j.ejmech.2021.113467. Epub 2021 Apr 15.
Emerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic. The antiviral activity was assessed against a structurally and phylogenetically diverse panel of RNA and DNA viruses from 25 species. Four compounds (11a-c, 12c) inhibited 4 DNA/RNA viruses with EC ≤ 20 μM. Toxicity of the compounds for the cell lines used for virus cultivation was negligible in most cases. In addition, previously reported and newly synthesized phenoxazine derivatives were evaluated against SARS-CoV-2, and some of them showed promising inhibition of reproduction with EC values in low micromolar range, although accompanied by commensurate cytotoxicity.
新兴和重现的病毒会定期在全球范围内引发爆发和流行，最终导致全球事件，如当前的新型严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）感染 COVID-19 大流行。因此，迫切需要新型抗病毒药物。在这里，我们展示了基于苯并恶嗪的核苷类似物的合成和抗病毒活性评估，分为三组：（1）8-烷氧基取代的，（2）无环的，和（3）碳环的。抗病毒活性针对来自 25 个物种的具有结构和系统发育多样性的 RNA 和 DNA 病毒进行评估。四种化合物（11a-c、12c）抑制了 4 种 DNA/RNA 病毒，EC 值≤20μM。在大多数情况下，用于病毒培养的细胞系对化合物的毒性可以忽略不计。此外，还评估了先前报道和新合成的苯并恶嗪衍生物对 SARS-CoV-2 的抑制作用，其中一些化合物在低微摩尔范围内显示出有希望的繁殖抑制作用，尽管伴随相应的细胞毒性。
