Analisis Potensi Senyawa Aktif Pulai (Alstonia scholaris) sebagai Inhibitor Enzim 3-Chymotrypsinlike Protease (EPI_ISL_576383) secara In Silico

Abstract

Coronavirus Disease (COVID-19) merupakan pandemik global yang disebabkan oleh infeksi SARS-CoV-2. Senyawa dengan aktivitas antivirus dapat dijadikan sebagai kandidat obat COVID-19 dengan menginhibisi enzim 3CLpro yang berperan penting dalam proses replikasi SARS-CoV-2. Alstonia scholaris memiliki senyawa aktif antivirus, namun potensinya sebagai inhibitor 3CLpro belum diketahui. Penelitian ini bertujuan menguji potensi senyawa aktif pulai sebagai inhibitor 3CLpro (EPI_ISL_576383) secara in silico. Penambatan molekuler yang dilakukan terhadap 75 ligan uji menunjukkan terdapat delapan ligan uji yang memiliki afinitas pengikatan yang lebih baik dibandingkan JRY7 dan dua ligan pembanding berdasarkan energi bebas Gibbs, konstanta disosiasi, dan interaksi terhadap residu penting, yaitu E-16-formyl-5α-methoxystrictamine, 17-Oacetylechitamine, nareline, alschomine, asam ursolik, nareline-metil-eter, 6-7- seco-angustilobin-B, dan picralinal. E-16-formyl-5α-methoxystrictamine merupakan senyawa penciri dari Alstonia scholaris yang menjadi ligan dengan energi bebas Gibbs dan konstanta disosiasi terendah (-6,0350 kkal/mol dan 0,0038x104 µM) yang berinteraksi dengan 11 residu penting di sisi aktif 3CLpro. Kata kunci: COVID-19, 3CLpro, Alstonia scholaris, in silico

Coronavirus Disease (COVID-19) is a global pandemic caused by infection with SARS-CoV-2. Compounds with antiviral activity were proposed to be candidates for the COVID-19 drug by inhibiting the 3CLpro enzyme which plays an important role in the SARS-CoV-2 replication process. Alstonia scholaris has antiviral active compounds but its potential as 3CLpro inhibitor is still unknown. This study aims to examine the potential of bioactive compounds of pulai as an inhibitor 3CLpro (EPI_ISL_576383) by in silico method. Molecular docking performed on 75 test ligands showed that there are eight test ligands that had better binding affinity than JRY7 and two comparison ligands based on the Gibbs free energy, dissociation constant, and interaction with important residue, namely E-16- formyl-5α-methoxystrictamine, 17-O-acetylechitamine, nareline, alschomine, ursolic acid, nareline-methyl-ether, 6-7-seco-angustilobine-B, and picralinal. E-16- formyl-5α-methoxystrictamine is the characteristic compound from Alstonia scholaris which demonstrate the lowest Gibbs free energy and dissociation constant (-6,0350 kcal/mol and 0,0038x104 µM) and has interaction with 11 important residu on the active site of 3CLpro. Keywords: COVID-19, 3CLpro, Alstonia scholaris, in silico