Schandock Franziska, Riber Camilla Frich, Röcker Annika, Müller Janis A, Harms Mirja, Gajda Paulina, Zuwala Kaja, Andersen Anna H F, Løvschall Kaja Borup, Tolstrup Martin, Kreppel Florian, Münch Jan, Zelikin Alexander N
Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark.
Adv Healthc Mater. 2017 Dec;6(23). doi: 10.1002/adhm.201700748. Epub 2017 Sep 25.
Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad-spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure-activity relationships for these pathogens in terms of their susceptibility to inhibition by polymers, and for polymers in terms of their anionic charge and hydrophobicity that make up broad-spectrum antiviral agents. The identified leads cannot be predicted based on prior data on polymer-based antivirals and represent promising candidates for further development as preventive microbicides.
病毒病原体继续给医疗保健和社会经济系统带来沉重负担。研发抗病毒药物的努力一再落后于病原体的出现,而且人们越来越认识到,广谱抗病毒药物将在未来的抗病毒工作中产生最大影响。这项工作筛选了合成聚合物作为新型广谱活性剂,并证明了这些聚合物对寨卡病毒、埃博拉病毒、拉沙热病毒、狂犬病病毒、马尔堡病毒、流感病毒、单纯疱疹病毒和人类免疫缺陷病毒具有活性。本文给出的结果从病原体对聚合物抑制的敏感性方面,以及从构成广谱抗病毒药物的聚合物的阴离子电荷和疏水性方面,提供了这些病原体的构效关系。基于先前关于聚合物基抗病毒药物的数据无法预测所确定的先导化合物,它们是作为预防性杀微生物剂进一步开发的有前景的候选物。