Abstract：
OBJECTIVE: The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus\'s main protease (Mpro), crucial for viral replication, is a promising strategy.
OBJECTIVE: The current study aims to discover novel inhibitors of Mpro.
METHODS: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound\'s toxicity was examined using the MTT assay on a human BJ cell line.
RESULTS: Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro\'s active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein\'s active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 μM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile.
CONCLUSIONS: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.
OBJECTIVE: The current study aims to discover novel inhibitors of Mpro.
METHODS: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound\'s toxicity was examined using the MTT assay on a human BJ cell line.
RESULTS: Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro\'s active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein\'s active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 μM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile.
CONCLUSIONS: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.
摘要：
目的：由新型SARS-CoV-2病毒引起的全球大流行强调了对治疗干预措施的迫切需要。靶向病毒的主要蛋白酶（Mpro），对病毒复制至关重要，是一个很有前途的策略。
目的：本研究旨在发现新型的Mpro抑制剂。
方法：当前研究确定了五种天然化合物（桃金娘酚B（C1），没药B(C2),儿茶素（C3），槲皮素（C4），通过虚拟筛选和计算方法，对Mpro具有很强的抑制潜力，预测它们的结合效率，并使用体外抑制活性进行验证。在人BJ细胞系上使用MTT测定法检查所选化合物的毒性。
结果：化合物C1表现出最高的结合亲和力，对接评分为-9.82kcal/mol，Mpro活性位点内强氢键相互作用。微尺度分子动力学模拟证实了化合物在蛋白质的活性口袋中的稳定性和紧密配合，显示出优越的结合相互作用。体外试验验证了它们的抑制作用，C1具有最显著的效力(IC50=2.85μM)。这些化合物在人BJ细胞系中的无毒性质也得到证实，提倡他们的安全形象。
结论：这些发现强调了结合计算和实验方法来鉴定SARS-CoV-2的潜在先导化合物的有效性，其中C1-C5正在成为针对该病毒的进一步药物开发的有希望的候选药物。
目的：本研究旨在发现新型的Mpro抑制剂。
方法：当前研究确定了五种天然化合物（桃金娘酚B（C1），没药B(C2),儿茶素（C3），槲皮素（C4），通过虚拟筛选和计算方法，对Mpro具有很强的抑制潜力，预测它们的结合效率，并使用体外抑制活性进行验证。在人BJ细胞系上使用MTT测定法检查所选化合物的毒性。
结果：化合物C1表现出最高的结合亲和力，对接评分为-9.82kcal/mol，Mpro活性位点内强氢键相互作用。微尺度分子动力学模拟证实了化合物在蛋白质的活性口袋中的稳定性和紧密配合，显示出优越的结合相互作用。体外试验验证了它们的抑制作用，C1具有最显著的效力(IC50=2.85μM)。这些化合物在人BJ细胞系中的无毒性质也得到证实，提倡他们的安全形象。
结论：这些发现强调了结合计算和实验方法来鉴定SARS-CoV-2的潜在先导化合物的有效性，其中C1-C5正在成为针对该病毒的进一步药物开发的有希望的候选药物。
