The interaction of alpha-mangostin and its derivatives against main protease enzyme in COVID-19 using in silico methods

• Main Authors: Syahrul Hidayat, Faisal Maulana Ibrahim, Kelvin Fernando Pratama, Muchtaridi Muchtaridi
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2021-01-01
• Series: Journal of Advanced Pharmaceutical Technology & Research
• Subjects: alpha-mangostin; covid-19; in silico; main protease
• Online Access: http://www.japtr.org/article.asp?issn=2231-4040;year=2021;volume=12;issue=3;spage=285;epage=290;aulast=Hidayat
• ISSN: 2231-4040; 0976-2094

More than 111 million people worldwide have been affected by the COVID-19 outbreak caused by SARS-CoV-2. The main therapeutic target of COVID-19 is main protease (Mpro). It plays a key role as an enzyme in the SARS-CoV-2 replication and transcription. In this case, the alpha-mangostin potentially has antiviral activity against Mpro by inhibiting this enzyme. Nevertheless, the alpha-mangostin has low solubility and a lack of information about alpha-mangostin activity against the SARS-CoV-2. The aim of this study is to describe the molecular interactions and identify the pharmacokinetics profile between alpha-mangostin and its derivatives. in silico study was conducted by pharmacokinetics and toxicity prediction, molecular docking simulation, and Lipinski's rule of five. FKS9 has a Gibbs free energy value of-10.5 kcal/mol with an inhibition constant of 36.45 μM and an interaction with amino acid His41 residue. Its human intestinal absorption and Caco-2 values were 95.13% and 47.71% while the plasma protein binding and blood-brain barrier values were 96.66% and 6.99%. FKS9 also has no mutagenic and carcinogenic potential. FKS9 as an alpha-mangostin derivative had the best interaction with the Mpro enzyme and its pharmacokinetic profiles was identified.