In-Silico molecular screening of natural compounds as a potential therapeutic inhibitor for Methicillin-resistant Staphylococcus aureus inhibition. (1st April 2023)

• Record Type: Journal Article
• Authors: Nandhini, Palanichamy; Gupta, Prashant Kr; Mahapatra, Arun Kumar; Das, Agneesh Pratim; Agarwal, Subhash Mohan; Mickymaray, Suresh; Alothaim, Abdulaziz S.; Rajan, Mariappan
• Is Part Of: Chemico-biological interactions. Volume 374(2023)
• Publication Date: 2023-04-01
• Subjects: Antibiotics -- Molecular docking studies -- Molecular dynamics -- MRSA Protein -- Natural products -- Inhibitors; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2023.110383
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening superbug causing infectious diseases such as pneumonia, endocarditis, osteomyelitis, etc. Conventional antibiotics are ineffective against MRSA infections due to their resistance mechanism against the antibiotics. The Penicillin Binding Protein (PBP2a) inhibits the activity of antibiotics by hydrolyzing the β-lactam ring. Thus, alternate treatment methods are needed for the treatment of MRSA infections. Natural bioactive compounds exhibit good inhibition efficiency against MRSA infections by hindering its enzymatic mechanism, efflux pump system, etc. The present work deals with identifying potential and non-toxic natural bioactive compounds (ligands) through molecular docking studies through StarDrop software. Various natural bioactive compounds which are effective against MRSA infections were docked with the protein (6VVA). The ligands having good binding energy values and pharmacokinetic and drug-likeness properties have been illustrated as potential ligands for treating MRSA infections. From this exploration, Luteolin, Kaempferol, Chlorogenic acid, Sinigrin, Zingiberene, 1-Methyl-4-(6-methylhepta-1, 5-dien-2-yl)cyclohex-1-ene, and Curcumin have found with good binding energies of −8.6 kcal/mol, −8.4 kcal/mol, −8.2 kcal/mol, −7.5 kcal/mol, −7.4 kcal/mol, −7.3 kcal/mol, and −7.2 kcal/mol, respectively. Graphical abstract: Image 1 Highlights: Natural bioactive compounds were docked against MRSA protein. Seven compounds were found with good pharmacokinetic properties, and binding energy. Kaempferol had attained stability after 20 ns, and luteolin after 50 ns in MD studies. Luteolin exhibited prolonged hydrogen bonding interaction with GLU180 (∼70%). Kaempferol showed the hydrogen bonding interaction with ASP124 upto 100 ns duration.