PHYLOGENETIC ANALYSIS AND SPIKE PROTEIN MUTATION PROFILING OF SARS-COV-2 VIRUS IN INDONESIA

• Main Author: Dian Pitaloka, Janice
• Format: Final Project
• Language: Indonesia
• Subjects: Ilmu hayati ; Biologi
• Online Access: https://digilib.itb.ac.id/gdl/view/79504
• Institution: Institut Teknologi Bandung

COVID-19 disease has been announced as a global pandemic on March 11, 2020, and spread to 223 countries including Indonesia, which was ranked the 14th country with most detected cases, with 4.235.384 total cases as of October 19, 2021. This disease is caused by the SARS-CoV-2 virus from the Coronaviridae family. SARS-CoV-2 has mutated, causing new variants to emerge including Variants of Concern (VOC) which can be characterized according to its spike protein (S) that interacts with the hACE2 receptor. This study intends to analyze the mutation profile of S protein in Indonesia from the beginning of the pandemic to June 17, 2021. The methods used in this study include S protein mutation analysis on 1.676 samples from Indonesia that were acquired through the GISAID database. Phylogenetic analysis was done by constructing a dataset, aligning them using MAFFT, trimming them with Gblocks, and constructing a phylogenetic tree using Mr. Bayes. Protein analysis was done through alignment with MAFFT, identification and selection of VOC mutations with an occurrence frequency of ? 1,85% in the data using CoV-GLUE, SWISS-MODEL homology modelling, mutagenesis in PyMOL, molecular docking with HDOCK, and MM/GBSA analysis. The results of this study showed that there were 26 variants of SARSCoV- 2 in Indonesia, including local variants (B.1.466.2 and B.1.470), and VOC Alfa, Beta, and Delta that were mostly found in Bali, DKI Jakarta, and West Java Provinces respectively. The N501Y mutation in VOC Alfa, Beta, Gamma, and the P681R mutation in VOC Delta showed positive effects on the interaction stability between S protein and hACE2 receptor, in which the two mutations had ??GBind scores above 0,5 kcal/mol. This showed that the two mutations had higher ?GBind scores compared to the Wuhan reference. Nevertheless, only the N501Y mutation showed an increase in hydrophobic interaction (100 interactions) when compared to the reference. Thus, the N501Y mutation from the Alfa, Beta, and Gamma variants, and the P681R mutation from the Delta variant had increased proteinreceptor complex stability caused by higher binding affinity and total hydrogenhydrophobic bond. This in silico study showed that the effects of the N501Y and P681R amino acid mutation pathways on the SARS-CoV-2 virus evolution in Indonesia need to be treated with caution because of their potential to cause the emergence of new variants which have higher infectivity and virulence.