Judul: Phylogenetic Studies and Their Relation to Oseltamivir and Zanamivir Resistance in Indonesian H1N1 Influenza Virus Isolates between 2009-2020
Abstrak: Pandemi virus H1N1 pada tahun 2009 menyerang hampir seluruh negara di dunia, termasuk Indonesia. Mutasi genetik menyebabkan munculnya strain virus baru yang memiliki kemampuan menyebar dengan cepat dan menyebabkan beberapa kelainan kesehatan pada penderita. Penelitian ini bertujuan melakukan studi filogenetik virus H1N1 isolat Indonesia pada tahun 2009-2020 untuk melihat asal penyebarannya serta kaitannya dengan resistensi terhadap obat antivirus oseltamivir dan zanamivir. Metode terdiri atas pengolahan data gen HA dan gen NA virus H1N1 isolat Indonesia, konstruksi pohon filogenetik, visualisasi pohon filogenetik, dilanjutkan dengan pensejajaran 25 sekuen protein NA dan HA. Hasil penelitian menunjukkan virus H1N1 yang ada di Indonesia memiliki kekerabatan paling dekat dengan isolat dari California dan Guangdong. Analisis pensejajaran sekuen protein menunjukkan adanya masing-masing satu mutasi pada H275Y, S247N, dan G249R. Mutasi pada H275Y dan S247N mengakibatkan virus mengalami resistensi terhadap antiviral oseltamivir, sedangkan mutasi pada G249R mengakibatkan virus mengalami resistensi terhadap zanamivir., The H1N1 virus pandemic in 2009 attacked almost all countries in the world, including Indonesia. Genetic mutations cause the emergence of new viral strains that have the ability to spread quickly and cause several health disorders in sufferers. This study aims to conduct a phylogenetic study of the H1N1 virus isolates from Indonesia in 2009- 2020 to see the origin of its spread and its relationship to resistance to the antiviral drugs oseltamivir and zanamivir. The method consisted of processing data on the HA and NA genes of the Indonesian H1N1 virus, construction of a phylogenetic tree, visualization of the phylogenetic tree, followed by the alignment of 25 NA and HA protein sequences. The results showed that the H1N1 virus in Indonesia had the closest kinship with isolates from California and Guangdong. Alignment protein analysis showed the presence of one mutation each in H275Y, S247N, and G249R. Mutations in H275Y and S247N caused the virus to develop resistance to the antiviral oseltamivir, while mutations in G249R caused the virus to develop resistance to zanamivir.
Keyword: phylogenetics, H1N1, hemagglutinin, mutation, neuraminidase, phylogenetics

Judul: Analisis In Silico Resistensi Mutasi G249R Protein Neuraminidase Virus H1N1 Isolat Indonesia terhadap Zanamivir dan Turunannya
Abstrak: 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.
Keyword: H1N1, mutation, neuraminidase, resistance, zanamivir

Judul: Metrik Einstein (Anti-) Self-Dual Berdimensi Empat dengan Metode Cartan
Abstrak: Gravitational field equation can be formulated in differential forms (differential geometry), which describes gravity as a manifestation of the curvature of space-time. Curvature of space-time is characterized by a metric that satisfies the gravitational field equation. With differential forms it can be formulated the (anti-) self-dual Einstein equation, which is a modification of the Cartan structure in (anti-) self-dual basis. Calculation of (anti-) self-dual metric with (anti-) self-dual Einstein equation is simpler than the calculation using Christoffel symbols.
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