The Profile of SARS-Cov-2 Genome from Indonesia and Its Impact on Paxlovid TM in Treating Covid-19

Hotma Martogi Lorensi Hutapea, Hotma Martogi Lorensi Hutapea, Yustinus Maladan, Tri Yunis Miko Wahyono, Arli Aditya Parikesit, Mondastri Korib Sudaryo

2023

Abstract

Since April 2023, PaxlovidTM has been used to treat SARS-CoV-2 infection in Indonesia. This medication contains 2 active compounds, ritonavir (RTV) and nirmatrelvir (NTV) that act as human CYP3A4 and viral main proteinase or 3CLPro respectively. NTV is novel drug to inhibit SARS-CoV-2 progressivity. Mutations that decrease NTV effectiveness have been reported in several countries, however, the data from Indonesia is still limited. We are using SARS-CoV-2 genomic data from GISAID which were collected from Sept 1, 2022 – Oct 31, 2023, from Indonesia. Any mutation in 3CLPro was recorded and then proceeded to be analysed further. NTV-3CLPro complex was downloaded from the Protein data bank (7SI9), and separated in PDB format. The 3CLPro was mutated using FOLDX to generate the mutant variant. Docking simulation was performed using Autodock Vina which is integrated into PyRx.0.9.7 software with SARS-CoV-2 Wuhan-Hu isolate (NC_045512.2) as control. RMSD score was calculated using YASARA software and considered valid if the redocking score is <2.0 Å. In total, 13,345 genomes from COVID-19 patients were submitted in GISAID, and all of them were Omicron, with GRA clade and XBB subvariant being more predominant. We found out that 3CLPro encoding genes were relatively conserved with only P132H mutation motive (99.8%) identified. Therefore, we performed the simulation on mutant P184L which was found in the Delta variant. Docking simulation demonstrated that the binding affinity score between nirmatrelvir and control was -8.6 kcal/mol, and -8.5 kcal/mol on 3CLPro mutant. According to the visualization of NTV-3CLPro interaction, the mutant P132 and P184 showed no difference compared to the control. We found no mutation that potentially decreased the effectiveness of PaxlovidTM based on the activity of NTV in the SARS-CoV-2 genome collected from patients in Indonesia. Therefore, SARS-CoV-2 in Indonesia might be susceptible to PaxlovidTM.

Paper Citation

in Harvard Style

Hutapea H., Maladan Y., Wahyono T., Parikesit A. and Sudaryo M. (2023). The Profile of SARS-Cov-2 Genome from Indonesia and Its Impact on Paxlovid TM in Treating Covid-19. In Proceedings of the 1st International Conference on Medical Science and Health - Volume 1: ICOMESH; ISBN 978-989-758-740-5, SciTePress, pages 32-37. DOI: 10.5220/0013217000003873

in Bibtex Style

@conference{icomesh23,
author={Hotma Martogi Lorensi Hutapea and Yustinus Maladan and Tri Yunis Miko Wahyono and Arli Aditya Parikesit and Mondastri Korib Sudaryo},
title={The Profile of SARS-Cov-2 Genome from Indonesia and Its Impact on Paxlovid TM in Treating Covid-19},
booktitle={Proceedings of the 1st International Conference on Medical Science and Health - Volume 1: ICOMESH},
year={2023},
pages={32-37},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0013217000003873},
isbn={978-989-758-740-5},
}

in EndNote Style

TY - CONF

JO - Proceedings of the 1st International Conference on Medical Science and Health - Volume 1: ICOMESH
TI - The Profile of SARS-Cov-2 Genome from Indonesia and Its Impact on Paxlovid TM in Treating Covid-19
SN - 978-989-758-740-5
AU - Hutapea H.
AU - Maladan Y.
AU - Wahyono T.
AU - Parikesit A.
AU - Sudaryo M.
PY - 2023
SP - 32
EP - 37
DO - 10.5220/0013217000003873
PB - SciTePress