Analisis In Silico Senyawa Aktif Tumbuhan Kayu Manis (Cinnamomum burmannii) sebagai Inhibitor 3C-Like Protease (3CLpro) SARS-CoV-2 di Indonesia

Abstract

Coronavirus disease 2019 (COVID-19) merupakan penyakit yang disebabkan virus SARS-CoV-2. Senyawa aktivitas antivirus berpotensi dapat menghambat enzim 3CLpro yang berperan dalam proses replikasi SARS-CoV-2. Kayu manis memiliki senyawa aktif antivirus, namun potensinya sebagai inhibitor 3CLpro belum diketahui. Penelitian ini bertujuan menganalisis potensi senyawa aktif kayu manis sebagai inhibitor 3CLpro (EPI_ISL_576383) secara in silico. Penambatan molekuler dengan autodock vina dilakukan terhadap 40 ligan uji menunjukkan sembilan ligan uji memiliki afinitas pengikatan lebih baik dibandingkan dengan JRY1 berdasarkan energi bebas Gibbs, konstanta inhibisi, dan interaksi terhadap residu penting, yaitu benzyl benzoate, caffeic acid, 3- phenylacetate, bornyl acetate, hydrocinnamic acid, eugenol, linalool, α-terpineol, dan 3-phenyl-2-propen-1-ol. Benzyl benzoate merupakan senyawa aktif dengan energi bebas Gibbs dan konstanta inhibisi terendah (-4,5 kkal/mol dan 0,498 µM) yang berinteraksi dengan 10 residu penting di sisi aktif 3CLpro. Linalool dan eugenol merupakan senyawa penciri kayu manis yang memiliki energi bebas Gibbs dan kontanta inhibisi (-3,6 kkal/mol dan 2,281 µM) berinteraksi dengan residu sisi aktif 3CLpro.

Coronavirus disease 2019 (COVID-19) is a disease caused by the SARSCoV-2 virus. Compounds with antiviral activity have the potential to inhibit the 3CLpro enzyme which plays a role in the SARS-CoV-2 replication process. Cinnamomun burmannii has antiviral active compounds but its potential as 3CLpro inhibitor is still unknown. This study aimed to analyze the potency of the active compound of cinnamon as an inhibitor 3CLpro (EPI_ISL_576383) by in silico method. Molecular docking with Autodock vina performed on 40 test ligands showed that nine test ligands had better binding affinity than JRY1 based on Gibbs free energy, inhibition constants, and interactions with important residues, namely benzyl benzoate, caffeic acid, 3-phenylacetate, bornyl acetate, hydrocinnamic acid, eugenol, linalool, α-terpineol, and 3-phenyl-2-propen-1-ol. Benzyl benzoate is the active compound with Gibbs free energy and lowest inhibition constant (-4.5 kcal/mol and 0.498 µM) which interacts with 10 important residues on the active site of 3CLpro. Linalool and eugenol are characteristic compounds of Cinnamomum burmannii which have Gibbs free energy and inhibition constants (-3.6 kcal/mol and 2.281 µM) that interact with the residue of active site 3CLpro