Analisis In Silico Resistensi Mutasi G249R Protein Neuraminidase Virus H1N1 Isolat Indonesia terhadap Zanamivir dan Turunannya

Abstract

Virus H1N1 menyerang manusia hampir seluruh negara di dunia, termasuk Indonesia menyebabkan pandemi pada tahun 2009. Mutasi pada asam amino neuraminidase virus menyebabkan resistensi terhadap obat antiviral. Penelitian ini bertujuan melakukan analisis in silico resistensi mutasi G249R pada protein neuraminidase virus H1N1 Isolat Indonesia terhadap zanamivir dan turunannya melalui analisis nilai energi ikatan, jenis ikatan kimia yang terbentuk, panjang ikatan, daerah pengikatan serta nilai Ki. Metode terdiri atas pemodelan struktur reseptor neuraminidase dari isolat Guangdong dan Indonesia, penambatan molekuler, visualisasi 2D dan 3D hasil penambatan molekuler, analisis nilai energi ikatan dan konstanta inhibisi. Hasil penelitian menunjukkan ligan-ligan yang dilakukan penambatan molekuler terhadap reseptor neuraminidase isolat California, Guangdong dan Indonesia berikatan dengan daerah pengikatan pada reseptor. Nilai energi ikatan dari hasil penambatan molekuler reseptor neuraminidase Isolat Indonesia dan Guangdong menunjukkan hasil yang lebih kecil dan nilai Ki yang dihasilkan lebih besar dibandingkan isolat California, menandakan adanya mutasi pada reseptor tersebut menyebabkan obat antiviral neuraminidase inhibitor kurang efektif dalam menghambat penyebaran virus H1N1 di wilayah tersebut.

The H1N1 virus attacks humans in almost all countries, including Indonesia causing a pandemic in 2009. Mutations in the viral amino acid neuraminidase cause resistance to antiviral drugs. This study aimed to conduct an in silico analysis of the resistance of the G249R mutation in the neuraminidase protein of the Indonesian isolate H1N1 virus to zanamivir and its derivatives through analysis of the bond energy value, type of chemical bond formed, bond length, binding area and Ki value. The method consisted of modelling the structure of neuraminidase receptors from Guangdong and Indonesia isolates, molecular anchoring, 2D and 3D visualization of molecular anchoring results, and analysis of bond energy values and inhibition constants. The results showed that the ligands that were molecularly bonded to the neuraminidase receptor isolates from California, Guangdong and Indonesia bind to the binding site on the receptor. The binding energy value from the results of molecular docking of the neuraminidase receptor. Indonesian and Guangdong isolates showed more minor effects, and the resulting Ki value was more significant than California isolates, indicating that a mutation in the receptor causes the antiviral neuraminidase inhibitor drugs to be less effective in inhibiting the spread of the H1N1 virus in the region.