Studi In Silico Senyawa Fenolik Madu sebagai Kandidat Inhibitor Mpro SARS-CoV-2
Authors: Ferdian Pamungkas Rizki , Elfirta Rizki Rabeca , Ikhwani Azra Zahrah Nadhirah , Kasirah Kasirah , Haerul Haerul , Sutardi Dodi , Ruhiat Gunawan 
Published: March 2022

SARS-CoV-2 has caused a global COVID-19 pandemic since late 2019 and the reported cases have not ended until now. One way to overcome the Covid-19 pandemic is to find the main viral protease inhibitor (Mpro) SARS-CoV-2 which is a key enzyme of virus replication. Honey is a bee-derived product that contains various phenolic compounds and has antiviral activity. This study aimed to find candidate Mpro SARS-CoV-2 inhibitors from honey phenolic compounds using molecular docking simulations in a directed manner. A total of 27 test ligands (from honey’s phenolic compounds), 4 comparison ligands (from synthetic antiviral compounds), and reference ligands (N3 compound) were screened for their character as drug compounds by Lipinski’s rules and for their toxicity by admetSAR. All ligands were docked to the Mpro SARS-CoV-2 receptor code 7BQY using AutoDock Tools 1.5.6 and Autodock Vina with center of coordinates: X = 10,398; Y = -1,254; Z = 23.473 and grid size: X = 40; Y = 46; Z = 40. Molecular docking simulation produces affinity energy and molecular interactions data. The results showed that the best candidate for Mpro SARS-CoV-2 inhibitor from honey’s phenolic compounds was genistein because it complied with all Lipinski rules, was non-toxigenic, not a carcinogen, had an affinity energy of -7.6 kCal/mol, 80% similarity to the reference ligand N3, and occupies 63,64% of the tethercoverage area. The results of this study are expected to be used in further research, both in vitro and in vivo.
Abstrak
SARS-CoV-2 menyebabkan pandemi COVID-19 secara global sejak akhir 2019 dan kasusnya dilaporkan belum berakhir sampai saat ini. Salah satu cara untuk mengatasi pandemi COVID-19 diantaranya dengan menemukan inhibitor main viral protease (Mpro) SARS-CoV-2 yang merupakan enzim kunci pada replikasi virus. Madu merupakan produk turunan lebah yang mengandung berbagai senyawa fenolik dan memiliki aktivitas antivirus. Penelitian ini bertujuan untuk menemukan kandidat inhibitor Mpro SARS-CoV-2 dari senyawa fenolik madu menggunakan simulasi penambatan molekuler secara terarah. Sebanyak 27 ligan uji (dari senyawa fenolik madu), 4 ligan pembanding (dari senyawa antiviral sintetik), dan ligan acuan (senyawa N3) diskrining karakternya sebagai senyawa obat dengan aturan Lipinski dan toksisitasnya dengan admetSAR. Semua ligan ditambatkan ke reseptor Mpro SARS-CoV-2 kode 7BQY menggunakan AutoDock Tools 1.5.6 dan Autodock Vina dengan pusat koordinat: X= 10,398; Y= -1,254; Z= 23,473 dan ukuran kisi: X= 40; Y= 46; Z= 40. Simulasi penambatan molekuler menghasilkan data energi afinitas dan interaksi molekuler. Hasil penelitian menunjukkan kandidat inhibitor Mpro SARSCoV-2 terbaik dari senyawa fenolik madu adalah genistein karena memenuhi semua aturan Lipinski, tidak toksik, bukan karsinogen, memiliki energi afinitas -7,6 kKal/mol, kemiripan 80% dengan ligan acuan N3, dan menempati 63,64% area cakupan penambatan. Hasil penelitian ini diharapkan dapat digunakan dalam penelitian selanjutnya, baik secara in vitro maupun in vivo.