Abstract

In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CL^pro/M^pro), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV M^pro), SARS-CoV main proteinase (SARS CoV 3CL^pro), and one human cellular transmembrane serine proteinase (TMPRSS2), was carried out. Except leucoanthocyanin all other phytochemicals proved better than all three positive control drugs against SARS-CoV main peptidase, whereas, flabelliferin was found to be the potential inhibitor for SARS-CoV main proteinase out performing all the positive control drugs and phytochemicals. Amongst the compounds studied, the best inhibitor for COVID-19 main protease was nelfinavir followed by flabelliferin and ocimin. Flabelliferin was found to the best promising inhibitor of human cellular transmembrane serine proteinase, followed by nelfinavir, curcumin, piperine and marmelosin. The result on the inhibition of human cellular transmembrane serine proteinase against COVID-19 has a stable therapeutic advantage as mutation may quickly occur on viral drug targets. Hence, all the phytochemicals tested in the present study are the potential inhibitors of the all the four drug targets and can form a part of therapeutics against COVID-19 with further clinical studies.

Communicated by Ramaswamy H. Sarma

摘要

对六种植物化学物质 flabelliferin、marmelosin、胡椒碱、 ocimin、姜黄素和无色花青素以及三种药物化合物奈非那韦、瑞德西韦和羟氯喹进行计算机分析，作为针对一种 SARS-CoV-2 病毒蛋白酶 COVID-19 的药物靶标的阳性对照主蛋白酶（SARS CoV-2 3CL ^pro /M ^pro），两种冠状病毒蛋白酶，SARS-CoV主肽酶（SARS CoV M ^pro），SARS-CoV主蛋白酶（SARS CoV 3CL ^{pro ）})，并进行了一种人细胞跨膜丝氨酸蛋白酶 (TMPRSS2)。除无色花青素外，所有其他植物化学物质均被证明优于所有三种针对 SARS-CoV 主要肽酶的阳性对照药物，而黄素福林被发现是 SARS-CoV 主要蛋白酶的潜在抑制剂，优于所有阳性对照药物和植物化学物质。在所研究的化合物中，对 COVID-19 主要蛋白酶的最佳抑制剂是奈非那韦，其次是 flabelliferin 和 ocimin。Flabelliferin 被发现是最有希望的人细胞跨膜丝氨酸蛋白酶抑制剂，其次是奈非那韦、姜黄素、胡椒碱和marmelosin。人细胞跨膜丝氨酸蛋白酶抑制 COVID-19 的结果具有稳定的治疗优势，因为突变可能很快发生在病毒药物靶点上。

由 Ramaswamy H. Sarma 传达