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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
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 s...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer India
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231289/ https://www.ncbi.nlm.nih.gov/pubmed/37363361 http://dx.doi.org/10.1007/s13337-023-00827-w |
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author | Gazali, Faris Muhammad Wijayanti, Nastiti Hakim, Mohamad Saifudin Supriyati, Endah Arguni, Eggi Daniwijaya, Marselinus Edwin Widyanto Nuryastuti, Titik Nuhamunada, Matin Nabilla, Rahma Haryana, Sofia Mubarika Wibawa, Tri |
author_facet | Gazali, Faris Muhammad Wijayanti, Nastiti Hakim, Mohamad Saifudin Supriyati, Endah Arguni, Eggi Daniwijaya, Marselinus Edwin Widyanto Nuryastuti, Titik Nuhamunada, Matin Nabilla, Rahma Haryana, Sofia Mubarika Wibawa, Tri |
author_sort | Gazali, Faris Muhammad |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-023-00827-w. |
format | Online Article Text |
id | pubmed-10231289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer India |
record_format | MEDLINE/PubMed |
spelling | pubmed-102312892023-06-01 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 Wijayanti, Nastiti Hakim, Mohamad Saifudin Supriyati, Endah Arguni, Eggi Daniwijaya, Marselinus Edwin Widyanto Nuryastuti, Titik Nuhamunada, Matin Nabilla, Rahma Haryana, Sofia Mubarika Wibawa, Tri Virusdisease Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-023-00827-w. Springer India 2023-05-31 2023-06 /pmc/articles/PMC10231289/ /pubmed/37363361 http://dx.doi.org/10.1007/s13337-023-00827-w Text en © The Author(s), under exclusive licence to Indian Virological Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
spellingShingle | Original Article Gazali, Faris Muhammad Wijayanti, Nastiti Hakim, Mohamad Saifudin Supriyati, Endah Arguni, Eggi Daniwijaya, Marselinus Edwin Widyanto Nuryastuti, Titik Nuhamunada, Matin Nabilla, Rahma Haryana, Sofia Mubarika Wibawa, Tri 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231289/ https://www.ncbi.nlm.nih.gov/pubmed/37363361 http://dx.doi.org/10.1007/s13337-023-00827-w |
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