大蓟内生真菌 Coniothyrium sp. DJ-1 抗 SARS-CoV-2 Mpro 活性的化学成分研究

作者：Zeng Jie-Chun; Yang Run; Huang Jin; Li Yan-Ping; Gao Lu; Wang Wei-Guang^*

来源：Chinese Traditional and Herbal Drugs, 2023, 54(10): 3071-3079.

DOI：10.7501/j.issn.0253-2670.2023.10.004

• 3-epi-dihydroaltenuene A
• antiviral activity
• Cirsium japonicum Fisch. ex DC
• Coniothyrium sp
• dihydroalterperylenol
• endophytic fungus
• SARS-CoV-2 Mpro
• secondary metabolites
• talaroflavone

Objective To study the chemical constituents with severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) inhibitory activity from Coniothyrium sp. DJ-1, an endophytic fungus isolated from Cirsium japonicum. Methods The strains and chemical constituents both with inhibitory activity were screened from thirty endophytic fungi by using 2019-nCoV Mpro/3CLpro inhibitor screening model. The secondary metabolites of the strain with high inhibition rate were separated and purified by normal phase silica gel column chromatography, reversed-phase RP-18 column chromatography, and HPLC. Their structures were identified by NMR, MS, and optical rotation data. And the compounds’ anti-SARS-CoV-2 Mpro activities were determined by fluorescence resonance energy transfer method. Results The Coniothyrium sp. DJ-1 strain with good inhibitory activity was screened from thirty endophytic fungi. Seventeen compounds were isolated from the rice fermentation extract of Coniothyrium sp. DJ-1, and identified as djalonensone (1), 5'-epialtenuene (2), altenuene (3), 4'-epialtenuene (4), 3-epi-dihydroaltenuene A (5), phialophoriol (6), 1-deoxyrubralactone (7), 6-hydroxy-8-methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (8), talaroflavone (9), altertoxin II (10), dihydroalterperylenol (11), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone (12), 7-hydroxy-2-hydroxymethyl-5-methyl-4H-chromen-4-one (13), tricycloalternarene 6b (14), tricycloalternarene D (15), 2-phenylethan-1-ol (16) and 4-hydroxybenzaldehyde (17). Compounds 5, 9 and 11 exhibited potent inhibitory effects on SARS-CoV-2 Mpro with IC50 values of 42.77, 25.85 and 24.26 μmol/L, respectively. Conclusion Compounds 1—15 and 17 have been isolated from the extracts of Coniothyrium sp. genus for the first time. Compounds 5, 9 and 11 exhibit potent inhibitory effects on SARS-CoV-2 Mpro. The research concludes that the method of screening active strains is helpful for us to quickly excavate active compounds from natural fungal products, moreover provides a basis for the research and development of drugs for COVID-19. ? 2023 Editorial Office of Chinese Traditional and Herbal Drugs.

• 单位
  云南中医药大学