The high mutation rate at the D614G hotspot-furin cleavage site region increases the priming efficiency of the Spike protein by furin protease: analysis of Indonesian SARS-CoV-2 G614 variants obtained during the early COVID-19 pandemic

Gazali, Faris Muhammad and Wijayanti, Nastiti and Hakim, Mohamad Saifudin and Supriyati, Endah and Arguni, Eggi and Daniwijaya, Marselinus Edwin Widyanto and Nuryastuti, Titik and Nuhamunada, Matin and Nabilla, Rahma and Haryana, Sofia Mubarika and Wibawa, Tri (2023) The high mutation rate at the D614G hotspot-furin cleavage site region increases the priming efficiency of the Spike protein by furin protease: analysis of Indonesian SARS-CoV-2 G614 variants obtained during the early COVID-19 pandemic. VirusDisease, 34 (2). 321 -330. ISSN 23473584

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Abstract

D614G mutation plays a significant role in the transmissibility of SARS-CoV-2. Identification of other mutations related to D614G mutation within the Spike protein is pivotal as they might contribute to the pathogenicity of SARS-CoV-2. This study aims to analyze the mutation rate of furin cleavage site (FCS) region of Indonesian origin SARS-CoV-2 and to predict the effect of mutation against Spike priming efficiency by furin. A total of 375 sequences of Indonesian isolates obtained during the early pandemic were used for mutation analysis. Mutation analysis includes mutation pattern, variability, frequency of mutation, amino acid conservation, and mutation rate. The effect of mutation against Spike priming efficiency by furin protease from eight sequences with mutation in the FCS region was analyzed by protein–protein docking. We showed that mutations related to the G614 variant were increasing through time, in contrast to the D614 variant. The FCS region at the position 675–692 contained the most variable (66.67) as well as the highest mutation frequency (85.92) and has been observed to be the hotspot mutations linked to the D614G mutation. The D614G hotspot-FCS region (residue 600–700) had the highest amino acid change per site (20.8) as well as the highest mutation rate as 1.34 × 10–2 substitution per site per year (95 CI 1.79 × 10–3–2.74 × 10–2), compared with other Spike protein regions. Mutations in the FCS region were the most common mutation found after the D614G mutation. These mutations were predicted to increase the Spike priming efficiency by furin. Thus, this study elucidates the importance of D614G mutation to other mutations located in the FCS region and their significance to Spike priming efficiency by furin. © 2023, The Author(s), under exclusive licence to Indian Virological Society.

Item Type: Article
Additional Information: Cited by: 2; All Open Access, Bronze Open Access
Uncontrolled Keywords: amino acid; complementary DNA; coronavirus spike glycoprotein; furin; virus DNA; amino acid composition; Article; binding affinity; coronavirus disease 2019; DNA sequencing; Indonesia; Markov chain Monte Carlo method; molecular clock; molecular docking; mutation rate; nonhuman; pandemic; protein cleavage; protein domain; protein protein interaction; reverse transcription polymerase chain reaction; Sanger sequencing; SARS-CoV-2 S (D614G) pseudotyped lentivirus; silent mutation; virus isolation; virus mutation
Subjects: R Medicine > RA Public aspects of medicine
R Medicine > RZ Other systems of medicine
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Maniso Maniso
Date Deposited: 22 Aug 2024 00:50
Last Modified: 22 Aug 2024 00:50
URI: https://ir.lib.ugm.ac.id/id/eprint/2750

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