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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Evolutionary and molecular characteristics of high-Shannon entropy codons in VP1 of Coxsackievirus A6
1Evidence-Based Medical Research Center, Mass Spectrometry Research Center for Diagnosis, Treatment, and Chronic Disease Rehabilitation, Jiangxi University of Chinese Medicine, Nanchang, PR China.
Abstract:
Coxsackievirus A6 (CVA6) has emerged as a predominant global pathogen of hand, foot and mouth disease, yet its evolutionary and molecular characteristics remain poorly understood. This study integrated 10 year molecular surveillance data from central China (2013-2024) with global CVA6 sequences to analyse high-entropy codons in the VP1 capsid protein and their co-evolution patterns. Phylogenetic and Bayesian evolutionary analyses indicated that CVA6 strains in China primarily clustered into sub-genotype D3, with an estimated global VP1 substitution rate of 3.62×10⁻³ substitutions/site/year. Shannon entropy analysis identified eight high-Shannon entropy codons in VP1 (sites 5, 29, 30, 97, 137, 174, 242, 283), with site 283 exhibiting the highest variability. A novel 283V variant (n=12) was uniquely detected in China after 2018. Direct-coupling analysis suggested co-evolution between residue pairs, most notably VP1-137 and VP1-242 (Direct information=0.44), where S137N may form new hydrogen bonds with 243 h, potentially contributing to structural changes that could influence immune evasion. Furthermore, S97N formed hydrogen bonds with D99, thereby altering the BC loop region. A spatiotemporal analysis showed that 283A replaced 283T on a global scale after 2017, while minor variants (e.g. 30D, 97I, 174A) exhibited localized circulation. These findings highlight the predominance of high-entropy codons in VP1 surface loops (BC, DE, EF and HI), suggesting ongoing adaptive selection pressure. Continuous genomic surveillance is imperative for tracking emerging variants (e.g. 283V, 97N) and for informing vaccine design against evolving CVA6 strains.
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