Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
Molecules. 2019 Sep 2;24(17):3184. doi: 10.3390/molecules24173184.
Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as "fleximers" have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.
由于能够抑制病毒 DNA 或 RNA 的复制，核苷类似物已被用作强效抗病毒治疗药物数十年。然而，核苷类似物的主要限制之一是抗病毒耐药性的发展。在这方面，多年来，被称为“fleximers”的灵活核苷类似物因其能够在酶结合部位探测不同的氨基酸而引起了关注，从而克服了潜在的抗病毒耐药性的发展。无环 fleximers 先前已证明对多种病毒具有抗病毒活性，包括中东呼吸综合征冠状病毒（MERS-CoV）、埃博拉病毒（EBOV），以及最近的登革热病毒（DENV）和黄热病病毒（YFV）等黄病毒。由于这些有趣的结果，进行了一项结构活性关系（SAR）研究，以分析嘧啶官能团和酰基保护基对抗病毒活性、细胞毒性和构象的影响。这些研究的结果在此呈现。
