论文标题
Carica Papaya叶提取物抑制SARS-COV-2主要蛋白酶，但不抑制人类TMPRSS2：一项体外和硅内研究
Carica papaya Leaf Extract Inhibits SARS-CoV-2 Main Proteases but not Human TMPRSS2: An In-vitro and In-silico Study
论文作者
论文摘要
Carica Papaya（CP）叶以其对登革热病毒和疟疾的传统药理作用而闻名。因此，CP也可能是治疗其他传染病（例如冠状病毒）的潜在解决方案。在这项研究中，我们评估了乙醇CP叶提取物在SARS-COV-2生命周期中抑制三种蛋白质靶点的酶活性的潜在影响，其中包括3-羟糖蛋白酶类蛋白酶（3CLPRO），PAPAIN样蛋白酶（PLPRO）和类蛋白质蛋白质蛋白蛋白蛋白蛋白2（Tmprsss）。结果表明，CP叶提取物分别用0.02微克/mL和0.06微克/mL抑制3Clpro和PLPRO，但对TMPRSS2不活跃。苯酚，2-甲基-5-（1,2,2-三甲基环丙基） - （s） - （17a）和β-甘露酸硫糖苷，Farnesyl-（21a）在提取物中使用GC-MS鉴定出来。在对接模拟过程中，这两种化合物比TMPRSS2表现出对主要蛋白酶的结合亲和力，这与Vitro研究一致。进一步的药效团图表明，17A的拟合评分高于SARS-COV-2 3CLPRO药效团模型，得出结论，CP叶提取物具有作为草药SARS-COV-2抗病毒剂的发展潜力。
Carica papaya (CP) leaf is long known for its traditional pharmacological effects against dengue virus and malaria. Therefore, CP could also be a potential solution for the treatment of other infectious diseases, such as coronavirus. In this study, we evaluate the potential effect of the ethanolic CP leaf extract in inhibiting the enzymatic activity of three protein targets in SARS-CoV-2 life cycle, which include the 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro) and the human transmembrane protein serine 2 (TMPRSS2). Results demonstrate that CP leaf extract inhibits 3CLpro and PLpro significantly with IC50 of 0.02 microgram/mL and 0.06 microgram/mL, respectively, but it is inactive towards TMPRSS2. Phenol, 2-methyl-5-(1,2,2-trimethylcyclopentyl)-(S)- (17a) and beta-mannofuranoside, farnesyl- (21a) were identified in the extract using GC-MS. These two compounds demonstrated a stronger binding affinity towards the main proteases than TMPRSS2 during the docking simulation, which agrees with the in-vitro study. Further pharmacophore mapping suggests that 17a has a fit score higher than 21a to the SARS-CoV-2 3CLpro pharmacophore model concluding that CP leaf extract has the potential to be developed as a herbal SARS-CoV-2 antiviral agent.
