A cystatin C similar protein from Musa acuminata that inhibits cathepsin B involved in rheumatoid arthritis using in silico approach and in vitro cathepsin B inhibition by protein extract

• Published in: Journal of biomolecular structure & dynamics 2023-12, Vol.ahead-of-print (ahead-of-print), p.1-14
• Main Authors: Rangra, Sabita, Chakraborty, Rajkumar, Hasija, Yasha, Aggarwal, Kamal Krishan
• Format: Article
• Language: English
• Subjects: cathepsin B; cystatin C; Molecular dynamics; Musa acuminata sp; plant protease inhibitor; Rheumatoid arthritis
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2023.2203234

Rheumatoid arthritis (RA) is an auto-immune disease that affects the synovial lining of the joints, causes synovitis and culminates to joint destruction. Cathepsin B is responsible for digesting unwanted proteins in extracellular matrix but its hyper expression could implicate in pathological diseases like RA. Available treatments for RA are classified into non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and steroids, but the severe side effects associated with these drugs is one of concerns and cannot be ignored. Thus, any alternative therapy with minimum or no side effects would be a cornerstone. In our in silico studies a cystatin C similar protein (CCSP) has been identified from Musa acuminata that could effectively inhibit the cathepsin B activity. In silico and molecular dynamics studies showed that the identified CCSP and cathepsin B complex has binding energy −66.89 kcal/mol as compared to cystatin C - cathepsin B complex with binding energy of −23.38 kcal/mol. These results indicate that CCSP from Musa acuminata has better affinity towards cathepsin B as compared to its natural inhibitor cystatin C. Hence, CCSP may be suggested as an alternative therapeutic in combating RA by inhibiting its one of the key proteases cathepsin B. Further, in vitro experiments with fractionated protein extracts from Musa sp. peel inhibited cathepsin B to 98.30% at 300 µg protein concentration and its IC 50 was found to be 45.92 µg indicating the presence of cathepsin B inhibitor(s) in protein extract of peel which was further confirmed by reverse zymography. Communicated by Ramaswamy H. Sarma HIGHLIGHTS Cathepsin B is one of the key protease involved in progression of RA disease and is regulated by endogenous inhibitor, cystatin C. The present study envisages the identification of cystatin C similar protein (CCSP) from Musa acuminata using an in silico approach. CCSP exhibit better affinity for cathepsin B as compared to cystatin C and may be suggested as an alternative dietary therapeutic(s) for RA. In vitro experiments indicated the presence of cathepsin B inhibitors in the peel extract of Musa sp.