SINTESIS, KARAKTERISASI STRUKTUR, DAN KAJIAN MOLECULAR DOCKING SENYAWA 4’-METOKSI FLAVONOL SEBAGAI INHIBITOR MAIN PROTEASE (MPro) SARS-CoV-2
Keywords:
flavonol, in silico, docking, SARS-CoV-2, 6M2N, main protease, Flavonol, in silico, docking, SARS-CoV-2, 6M2NAbstract
Main protease (MPro) merupakan salah satu protein yang memiliki peran penting dalam proses replikasi virus SARS-CoV-2. Beberapa studi in silico dan in vitro telah menunjukkan bahwa senyawa flavonoid baik alami maupun sintetis memiliki potensi yang menjanjikan untuk dikembangkan sebagai antivirus SARS-CoV-2. Penelitian ini bertujuan untuk mensintesis senyawa 4'-metoksi flavonol dan mengeksplorasi potensinya sebagai inhibitor MPro SARS-CoV-2. Sintesis dilakukan menggunakan senyawa awal 2'-hidroksi-4-metoksi kalkon melalui reaksi Algar-Flynn-Oyamada (AFO) dengan metode pengadukan (stirring method). Selanjutnya, kajian molecular docking dilakukan menggunakan struktur kristal MPro SARS-CoV-2 yang diunduh dari website RCSB Protein Data Bank (PDB ID: 6M2N). Hasil sintesis senyawa 4'-metoksi flavonol diperoleh rendemen produk sebesar 37,72 % dan struktur produk hasil sintesis telah dikonfirmasi melalui analisis spektroskopi UV-Vis, FT-IR, dan 1H NMR. Selanjutnya, hasil kajian molecular docking menunjukkan bahwa senyawa 4’-metoksi flavonol dapat membentuk ikatan hidrogen dengan dua residu penting pada sisi aktif 6M2N, yaitu Glu166 dan Gln189, dengan nilai energi bebas ikatan sebesar -7,13 kcal/mol dan nilai RMSD sebesar 1,45. Hasil kajian ini menunjukkan bahwa senyawa 4'-metoksi flavonol dapat terikat dengan lebih mudah pada sisi aktif MPro SARS-CoV-2 dibandingkan dengan baicalein sebagai senyawa flavonoid pembanding yang telah terbukti secara in vitro dapat menghambat aktivitas proteolitik MPro SARS-CoV-2.
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