HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy.
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life-12-00417-v3.pdf
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1.72 MB
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Resource type
Journal article
Date published
March 12, 2022
Abstract
In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16β,17-diol (5), crotocorylifuran (6), lupeol (7), betulin (8), and ellagic acid (9) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 μg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A (10) and urolithin B (11) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1–9, urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG −5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG −4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg2+ ion in the active site.
Journal title
Life
Volume
12
Issue
3
Article number
417
Publisher
MDPI AG
Place of publication
Basel, Switzerland
eISSN
2075-1729
Date accepted
March 9, 2022
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In Copyright
Additional information
This article belongs to the Section Plant Science.