Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, USA.
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Sci Rep. 2022 Jan 31;12(1):1641. doi: 10.1038/s41598-022-05580-6.
H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. The H84T BanLec EC was 0.025 µM for VZV (SI = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI = 441) in HFFs, and 0.33 µM for HSV-1 (SI = 308) in Vero cells. Human skin was obtained from reduction mammoplasties and prepared for culture. Skin was infected and cultured up to 14 days. H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. Additionally, H84T BanLec arrested virus spread when treatment was delayed. Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. This is the first demonstration of H84T BanLec effectiveness against DNA viruses. H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses.
H84T BanLec 是一种从香蕉中克隆出来的具有广谱抗病毒活性的分子工程化凝集素，可针对多种 RNA 病毒发挥作用。H84T BanLec 二聚体结合病毒包膜上含有高甘露糖 N-聚糖的糖蛋白，从而阻止病毒附着、进入、脱壳和扩散。目前尚不清楚 H84T BanLec 是否对人类疱疹病毒水痘带状疱疹病毒（VZV）、人类巨细胞病毒（HCMV）和单纯疱疹病毒 1 型（HSV-1）有效，因为这些病毒在其包膜上表达高甘露糖 N 连接糖蛋白。我们在细胞、皮肤器官培养物和小鼠中评估了 H84T BanLec 对 VZV-ORF57-Luc、TB40/E HCMV-fLuc-eGFP 和 HSV-1 R8411 的作用。在人包皮成纤维细胞（HFFs）中，H84T BanLec 对 VZV 的 EC 为 0.025µM（SI=4000），在 HFFs 中对 HCMV 的 EC 为 0.23µM（SI=441），在 Vero 细胞中对 HSV-1 的 EC 为 0.33µM（SI=308）。从乳房缩小术获得人类皮肤，并准备用于培养。对皮肤进行感染并培养至 14 天。在培养基中，浓度为 10µM 的 H84T BanLec 可预防 VZV、HCMV 和 HSV-1 在皮肤中的扩散，并且还表现出剂量依赖性的抗病毒作用。此外，当治疗延迟时，H84T BanLec 可阻止病毒传播。当 H84T BanLec 存在于培养基中时，感染 HCMV 的皮肤的组织病理学检查未显示出明显的毒性。在带有人类皮肤异种移植物的无胸腺裸鼠（NuSkin 小鼠）中，H84T BanLec 在皮下注射前进行皮内病毒接种，可减少 VZV 的扩散。这是 H84T BanLec 对 DNA 病毒有效性的首次证明。H84T BanLec 可能对其他具有临床相关性的糖基化病毒具有额外的未被探索的活性。
