Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense

Pan, Bo Wen1; Xiao, Jun Wei1; Li, Su Mei2; Yang, Xin1; Zhou, Xia1; Sun, Qing Wen1; Chen, Mei1; Xie, Shou Xia2; Sakharkar, Meena Kishore3; Yang, Jian3; Zhou, Ying1; Wei, Ying1

2022-12-01

10.3390/ph15121499

PHARMACEUTICALS   Impact Factor & Quartile

1424-8247

Hypericum kouytchense Levl is a semi-evergreen plant of the Hypericaceae family. Its roots and seeds have been used in a number of traditional remedies for antipyretic, detoxification, anti-inflammatory, antimicrobial and antiviral functions. However, to date, no bioactivity compounds have been characterized from the insect gall of H. kouytchens. In this study, we evaluated the antiviral activities of different extracts from the insect gall of H. kouytchen against cathepsin L, HIV-1 and renin proteases and identified the active ingredients using UPLC-HRMS. Four different polar extracts (HW, H30, H60 and H85) of the H. kouytchense insect gall exhibited antiviral activities with IC50 values of 10.0, 4.0, 3.2 and 17.0 mu g/mL against HIV-1 protease; 210.0, 34.0, 24.0 and 30.0 mu g/mL against cathepsin L protease; and 180.0, 65.0, 44.0 and 39.0 mu g/mL against human renin, respectively. Ten compounds were identified and quantified in the H. kouytchense insect gall extracts. Epicatechin, eriodictyol and naringenin chalcone were major ingredients in the extracts with contents ranging from 3.9 to 479.2 mu g/mg. For HIV-1 protease, seven compounds showed more than 65% inhibition at a concentration of 1000.0 mu g/mL, especially for hypericin and naringenin chalcone with IC50 values of 1.8 and 33.0 mu g/mL, respectively. However, only hypericin was active against cathepsin L protease with an IC50 value of 17100.0 mu g/mL, and its contents were from 0.99 to 11.65 mu g/mg. Furthermore, we attempted to pinpoint the interactions between the active compounds and the proteases using molecular docking analysis. Our current results imply that the extracts and active ingredients could be further formulated and/or developed for potential prevention and treatment of HIV or SARS-CoV-2 infections.

Hypericum kouytchense active ingredient UPLC-HRMS HIV-1 protease cathepsin L protease molecular docking

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Innovation Group Project of Guizhou Province[Qian Jiao He KY (2021) 018] ; Guizhou Provincial Science and Technology Projects["Qian Ke He Zhi Cheng (2020) 4Y213","ZK (2022) general480"] ; Research Center of Molecular Bioactivity from Traditional Chinese Medicine and Ethnomedicine[3411-4110000520364] ; Innovative and Entrepreneurial Project of Guizhou University of Traditional Chinese Medicine[2019(56)] ; Shenzhen Fund for Guangdong Provincial High-Level Clinical Key Specialties[SZXK059] ; Youth Science and Technology Talent Growth Project of Guizhou Province[Qian Jiao He KY (2022) 253] ; Project of Guizhou Provincial Health Commission["gzwkj2022-232","gzwkj2022-467"]

Pharmacology & Pharmacy

Chemistry, Medicinal ; Pharmacology & Pharmacy

WOS:000904250100001

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Web of Science

1.Guizhou Univ Tradit Chinese Med, Coll Pharm, Guiyang 550025, Peoples R China
2.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp,Dept Pharmacol, Shenzhen 518020, Peoples R China
3.Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5E5, Canada

Pan, Bo Wen,Xiao, Jun Wei,Li, Su Mei,et al. Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense[J]. PHARMACEUTICALS,2022,15(12).

Pan, Bo Wen.,Xiao, Jun Wei.,Li, Su Mei.,Yang, Xin.,Zhou, Xia.,...&Wei, Ying.(2022).Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense.PHARMACEUTICALS,15(12).

Pan, Bo Wen,et al."Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense".PHARMACEUTICALS 15.12(2022).