D614G热点-furin切割位点区域的高突变率提高了furin蛋白酶对Spike蛋白的引物效率:对COVID-19大流行早期获得的印度尼西亚SARS-CoV-2 G614变异体的分析

Q2 Medicine

VirusDisease Pub Date : 2023-05-31 DOI:10.1007/s13337-023-00827-w

Faris Muhammad Gazali, Nastiti Wijayanti, Mohamad Saifudin Hakim, Endah Supriyati, Eggi Arguni, Marselinus Edwin Widyanto Daniwijaya, Titik Nuryastuti, Matin Nuhamunada, Rahma Nabilla, Sofia Mubarika Haryana, Tri Wibawa

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引用次数: 1

摘要

D614G突变在SARS-CoV-2的传播性中起重要作用。鉴定刺突蛋白中与D614G突变相关的其他突变至关重要，因为它们可能与SARS-CoV-2的致病性有关。本研究旨在分析印尼源SARS-CoV-2的furin裂解位点(FCS)区突变率，并预测突变对furin引穗效率的影响。在大流行早期获得的总共375个印度尼西亚分离株序列用于突变分析。突变分析包括突变模式、变异、突变频率、氨基酸守恒和突变率。通过蛋白对接分析了8个FCS区突变序列对furin蛋白酶引穗效率的影响。我们发现，与D614变体相反，与G614变体相关的突变随着时间的推移而增加。675 ~ 692位置的FCS区变异最多(66.67%)，突变频率最高(85.92%)，是D614G突变相关的热点突变。D614G热点- fcs区(残基600 ~ 700)与其他穗蛋白区相比，每个位点的氨基酸变化最高(20.8%)，突变率最高，为1.34 × 10-2替换/年(95% CI 1.79 × 10-3-2.74 × 10-2)。在D614G突变之后，FCS区域的突变是最常见的突变。预计这些突变可以通过furin提高Spike启动效率。因此，本研究阐明了D614G突变对位于FCS区域的其他突变的重要性，以及它们对furin引发Spike效率的意义。补充信息:在线版本包含补充资料，下载地址:10.1007/s13337-023-00827-w。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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.

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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.

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来源期刊

VirusDisease Medicine-Infectious Diseases

CiteScore

7.00

自引率

0.00%

发文量

期刊介绍： VirusDisease, formerly known as ''Indian Journal of Virology'', publishes original research on all aspects of viruses infecting animal, human, plant, fish and other living organisms.