Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30310, USA.
Malango Traditional Healers Association, Fatick, Senegal.
Virol J. 2023 Mar 22;20(1):50. doi: 10.1186/s12985-023-02010-5.
Plants are used in traditional healing practices of many cultures worldwide. Momordica balsamina is a plant commonly used by traditional African healers as a part of a treatment for HIV/AIDS. It is typically given as a tea to patients with HIV/AIDS. Water-soluble extracts of this plant were found to contain anti-HIV activity.
We employed cell-based infectivity assays, surface plasmon resonance, and a molecular-cell model of the gp120-CD4 interaction to study the mechanism of action of the MoMo30-plant protein. Using Edman degradation results of the 15 N-terminal amino acids, we determined the gene sequence of the MoMo30-plant protein from an RNAseq library from total RNA extracted from Momordica balsamina.
Here, we identify the active ingredient of water extracts of the leaves of Momordica balsamina as a 30 kDa protein we call MoMo30-plant. We have identified the gene for MoMo30 and found it is homologous to a group of plant lectins known as Hevamine A-like proteins. MoMo30-plant is distinct from other proteins previously reported agents from the Momordica species, such as ribosome-inactivating proteins such as MAP30 and Balsamin. MoMo30-plant binds to gp120 through its glycan groups and functions as a lectin or carbohydrate-binding agent (CBA). It inhibits HIV-1 at nanomolar levels and has minimal cellular toxicity at inhibitory levels.
CBAs like MoMo30 can bind to glycans on the surface of the enveloped glycoprotein of HIV (gp120) and block entry. Exposure to CBAs has two effects on the virus. First, it blocks infection of susceptible cells. Secondly, MoMo30 drives the selection of viruses with altered glycosylation patterns, potentially altering their immunogenicity. Such an agent could represent a change in the treatment strategy for HIV/AIDS that allows a rapid reduction in viral loads while selecting for an underglycosylated virus, potentially facilitating the host immune response.
植物被广泛应用于世界各地多种文化的传统医疗实践中。非洲传统医学中常用苦瓜来治疗艾滋病毒/艾滋病。通常将苦瓜制成茶给艾滋病毒/艾滋病患者服用。研究发现,这种植物的水溶性提取物具有抗艾滋病毒的活性。
我们采用基于细胞的感染性测定、表面等离子体共振和 gp120-CD4 相互作用的分子细胞模型,研究 MoMo30-植物蛋白的作用机制。根据 15 N 端氨基酸的 Edman 降解结果,我们从苦瓜总 RNA 提取的 RNAseq 文库中确定了 MoMo30-植物蛋白的基因序列。
在这里,我们确定了苦瓜叶水提物的活性成分是一种 30 kDa 的蛋白质,我们称之为 MoMo30-植物。我们已经鉴定出 MoMo30 的基因,并发现它与一组被称为 Hevamine A 样蛋白的植物凝集素同源。MoMo30-plant 与以前从苦瓜属报道的其他蛋白(如核糖体失活蛋白 MAP30 和 Balsamin)不同。MoMo30-plant 通过其糖基结合 gp120,并作为凝集素或碳水化合物结合剂 (CBA) 发挥作用。它以纳摩尔级别的浓度抑制 HIV-1,在抑制水平下具有最小的细胞毒性。
像 MoMo30 这样的 CBA 可以与 HIV 包膜糖蛋白 (gp120) 表面的聚糖结合并阻断进入。暴露于 CBA 对病毒有两种影响。首先,它阻止易感细胞的感染。其次,MoMo30 驱动糖基化模式改变的病毒选择,可能改变其免疫原性。这种药物可能代表 HIV/AIDS 治疗策略的改变,它允许迅速降低病毒载量,同时选择低聚糖的病毒,从而可能促进宿主免疫反应。