Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest arisen contagious respiratory pathogen related to the global outbreak of atypical pneumonia pandemic (COVID-19). The essential oils (EOs) of Eucalyptus camaldulensis, E. ficifolia F. Muell., E. citriodora Hook, E. globulus Labill, E. sideroxylon Cunn. ex Woolls, and E. torquata Luehm. were investigated for its antiviral activity against SARS-CoV-2. The EOs phytochemical composition was determined using GC/MS analysis. Correlation with the explored antiviral activity was also studied using multi-variate data analysis and Pearson’s correlation. The antiviral MTT and cytopathic effect inhibition assays revealed very potent and promising anti SARS-CoV-2 potential for E. citriodora EO (IC₅₀ = 0.00019 µg/mL and SI = 26.27). The multivariate analysis revealed α-pinene, α-terpinyl acetate, globulol, γ -terpinene, and pinocarvone were the main biomarkers for E. citriodora oil. Pearson’s correlation revealed that globulol is the top positively correlated compound in E. citriodora oil to its newly explored potent anti SARS-CoV-2 potential. A molecular simulation was performed on globulol via docking in the main active sites of both SARS-CoV-2 viral main protease (Mpro) and spike protein (S). In silico predictive ADMET study was also developed to investigate the pharmacokinetic profile and predict globulol toxicity. The obtained in silico, in vitro and Pearson’s correlation results were aligned showing promising SARS-CoV-2 inhibitory activity of E. citriodora and globulol. This study is a first record for E. citriodora EO as a novel lead exhibiting potent in vitro, and in silico anti SARS-CoV-2 potential and suggesting its component globulol as a promising candidate for further extensive in silico, in vitro and in vivo anti-COVID studies.

中文翻译：

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桉树油的植物化学成分与其新探索的抗 SARS-CoV-2 潜力相关：体外和计算机方法

摘要

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是与全球非典型肺炎大流行（COVID-19）爆发相关的最新出现的传染性呼吸道病原体。赤桉、F. Muell.、柠檬桉、蓝桉、铁木桉的精油 (EO) 。ex Woolls 和E. torquata Luehm。对其针对 SARS-CoV-2 的抗病毒活性进行了研究。使用 GC/MS 分析测定 EO 植物化学成分。还使用多变量数据分析和皮尔逊相关性研究了与所探索的抗病毒活性的相关性。抗病毒 MTT 和细胞病变效应抑制测定显示E. citriodora EO 具有非常有效且有前景的抗 SARS-CoV-2 潜力（IC ₅₀  = 0.00019 µg/mL，SI = 26.27）。多变量分析显示α-蒎烯、α-乙酸松油酯、球醇、γ-松油烯和松香芹酮是柠檬香精油的主要生物标志物。Pearson 的相关性表明，球洛醇是柠檬桉油中与其新发现的有效抗 SARS-CoV-2 潜力呈正相关的最重要化合物。通过对接 SARS-CoV-2 病毒主蛋白酶 (Mpro) 和刺突蛋白 (S) 的主要活性位点，对球洛尔进行了分子模拟。还开发了计算机预测 ADMET 研究来研究药代动力学特征并预测球洛尔毒性。计算机模拟、体外实验和 Pearson 相关结果一致，显示E. citriodora和 globulol 具有良好的 SARS-CoV-2 抑制活性。这项研究首次记录了E. citriodora EO 作为一种新型先导化合物，在体外和计算机模拟中表现出有效的抗 SARS-CoV-2 潜力，并表明其成分 globulol 作为进一步广泛的计算机模拟、体外和体内研究的有希望的候选者。抗新冠病毒研究。