Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.
Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.
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DOI：
10.1021/acs.jnatprod.1c01003
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发表时间：
2022-04-22
影响因子：
5.1
通讯作者：
Xiao, Wei-Lie
中科院分区：
文献类型：
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作者：
Liang, Xin-Xin;Zhang, Xing-Jie;Xiao, Wei-Lie
从内生真菌枝孢霉的培养物中分离得到8个新的阿斯普维酮类似物，阿斯普尔文素A-H(1-8)和阿斯普维林酮D、M、O和R(9-12)。7951号。进行了详细的光谱分析，确定了新化合物的结构。其中化合物9、10和12对SARS冠状病毒2M(PRO)有不同程度的抑制作用，IC50值分别为10.3+/-0.6、9.4+/-0.6和7.7+/-0.6 mM。除3和4外，其余化合物均通过抑制乳酸脱氢酶(LDH)的释放而发挥抗炎活性，IC50值在0.7~7.4mU之间。化合物10通过抑制Casp-1裂解、IL-1β成熟、NLRP3炎性小体激活和下垂而显示出最强的抗炎活性。研究结果表明，阿斯普维酮类似物9、10和12可能是治疗2019年冠状病毒病(新冠肺炎)的有前途的候选药物，因为它们抑制SARS-CoV-2感染，减少SARS-CoV-2引起的炎症反应。
Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M-pro) at 10 mu M. Notably, compounds 9, 10, and 12 showed potential SARSCoV-2M(pro) inhibition with IC50 values of 10.3 +/- 0.6, 9.4 +/- 0.6, and 7.7 +/- 0.6 mM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 mu M. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1 beta maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.