Naturally occurring organosulfur compounds effectively inhibits PCSK-9 activity and restrict PCSK-9-LDL-receptor interaction via <i>in-silico</i> and <i>in-vitro</i> approach
Parvej Ahmad, Sahir Sultan Alvi, Mohd Waiz, M. S. Khan, Mohd Shahnawaz Khan, Saheem Ahmad, M. Salman Khan, M. Salman Khan
Abstract
The present study intended to divulge the potential role of garlic-derived organosulfur compounds (OSCs) in targeting PCSK-9 and averting its interaction with the EGF-A portion of LDL-R via in-vitro and in-silico analysis. Our in-silico screening data showed that 3-(Propylsulfinyl)-L-alanine (PSA), S-Ethyl-L-cysteine (SEC), alliin, and S-Allyl-L-cysteine (SAC) exhibited higher binding energy (−7.05, −7.00, −6.65, and −6.31 Kcal/mol, respectively) against PCSK-9, among other selected OSCs. Further, the protein-protein interaction study of PCSK-9-OSCs-complex with EGF-A demonstrated a similar binding pattern with E-total values ranging from −430.01 to −405.6 Kcal/mol. These results were further validated via in-vitro analysis which showed that SEC, SAC, and diallyl trisulphide (DAT) exhibited the lowest IC50 values of 4.70, 5.26, and 5.29 µg/mL, respectively. In conclusion, the presented data illustrated that SEC, SAC, and DAT were the best inhibitors of PCSK-9 activity and may have the potential to improve the LDL-R function and lower the circulatory LDL-C level.