Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India.
J Mol Model. 2023 Mar 6;29(4):88. doi: 10.1007/s00894-023-05487-7.
Crimean-Congo haemorrhagic fever virus (CCHFV) has tripartite RNA genome and is endemic in various countries of Asia, Africa and Europe.
The present study is focused on mutation profiling of CCHFV L segment and phylogenetic clustering of protein dataset into six CCHFV genotypes.
Phylogenetic tree rooted with NCBI reference sequence (YP_325663.1) indicated less divergence from genotype III and the sequences belonging to same genotypes have shown less divergence among each other. Mutation frequency at 729 mutated positions was calculated and 563, 49, 33, 46 and 38 amino acid positions were found to be mutated at mutation frequency intervals of 0-0.2, 0.21-0.4, 0.41-0.6, 0.61-0.8 and 0.81-1.0 respectively. Thirty-eight highly frequent mutations (0.81-1.0 interval) were found in all genotypes and mapping in L segment (encoded for RdRp) revealed four mutations (V2074I, I2134T/A, V2148A and Q2695H/R) in catalytic site domain and no mutation in OTU domain. Molecular dynamic simulation and in silico analysis showed that catalytic site domain displayed large deviation and fluctuation upon introduction of these point mutations.
Overall study provides strong evidence that OTU domain is highly conserved and less prone to mutation whereas point mutations recorded in catalytic domain have affected the stability of protein and were found to be persistent in the large population.
克里米亚-刚果出血热病毒（CCHFV）具有三分体 RNA 基因组，在亚洲、非洲和欧洲的多个国家流行。
本研究集中于 CCHFV L 片段的突变分析，并对蛋白数据集进行系统发育聚类，分为六个 CCHFV 基因型。
以 NCBI 参考序列（YP_325663.1）为根的系统发育树显示与基因型 III 的差异较小，属于同一基因型的序列彼此之间的差异较小。计算了 729 个突变位置的突变频率，发现 563、49、33、46 和 38 个氨基酸位置的突变频率在 0-0.2、0.21-0.4、0.41-0.6、0.61-0.8 和 0.81-1.0 之间。所有基因型都发现了 38 个高频突变（0.81-1.0 区间），并在 L 片段（编码 RdRp）中定位，在催化位点结构域发现了四个突变（V2074I、I2134T/A、V2148A 和 Q2695H/R），而 OTU 结构域没有突变。分子动力学模拟和计算机分析表明，引入这些点突变后，催化位点结构域显示出较大的偏差和波动。
总体研究结果提供了强有力的证据，表明 OTU 结构域高度保守，不易发生突变，而在催化结构域记录的点突变影响了蛋白质的稳定性，并在大群体中发现具有持续性。
