Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Immunobiology, R. Weigla Str. 12, 53-114 Wrocław, Poland.
Institute of Organic Chemistry, Lodz University of Technology, S. Żeromskiego Str. 116, 90-924 Łódź, Poland.
Molecules. 2022 May 31;27(11):3552. doi: 10.3390/molecules27113552.
The core of Cyclolinopeptide A (CLA, cyclo(LIILVPPFF)), responsible for its high immunosuppressive activity, contains a Pro-Pro-Phe-Phe sequence. A newly synthesized cyclic tetrapeptide, cyclo(Pro-Pro--HoPhe-Phe) (denoted as 4B8M) bearing the active sequence of CLA, was recently shown to exhibit a wide array of anti-inflammatory properties in mouse models. In this investigation, we demonstrate that the peptide significantly inhibits the replication of human adenovirus C serotype 5 (HAdV-5) and virus type-1 (HSV-1) in epithelial lung cell line A-549, applying Cidofovir and Acyclovir as reference drugs. Based on a previously established mechanism of its action, we propose that the peptide may inhibit virus replication by the induction of PGE2 acting via EP2/EP4 receptors in epithelial cells. In summary, we reveal a new, antiviral property of this anti-inflammatory peptide.
环六肽 A（CLA，环（LIILVPPFF））的核心区域负责其高免疫抑制活性，其中包含一个 Pro-Pro-Phe-Phe 序列。最近，一种新合成的环状四肽，环（Pro-Pro--HoPhe-Phe）（表示为 4B8M），具有 CLA 的活性序列，在小鼠模型中表现出广泛的抗炎特性。在本研究中，我们证明该肽可显著抑制人腺病毒 C 血清型 5（HAdV-5）和单纯疱疹病毒 1 型（HSV-1）在肺上皮细胞系 A-549 中的复制，以西多福韦和阿昔洛韦作为参考药物。基于其作用机制的先前建立，我们提出该肽可能通过诱导 PGE2 发挥作用，通过上皮细胞中的 EP2/EP4 受体抑制病毒复制。综上所述，我们揭示了这种抗炎肽的新的抗病毒特性。
