Roy Ayan, Guo Fucheng, Singh Bhupender, Gupta Shelly, Paul Karan, Chen Xiaoyuan, Sharma Neeta Raj, Jaishee Nishika, Irwin David M, Shen Yongyi
Department of Biotechnology, Lovely Professional University, Phagwara, India.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Front Microbiol. 2021 Apr 6;12:548275. doi: 10.3389/fmicb.2021.548275. eCollection 2021.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly all over the world and has raised grave concern globally. The present research aims to conduct a robust base compositional analysis of SARS-CoV-2 to reveal adaptive intricacies to the human host. Multivariate statistical analysis revealed a complex interplay of various factors including compositional constraint, natural selection, length of viral coding sequences, hydropathicity, and aromaticity of the viral gene products that are operational to codon usage patterns, with compositional bias being the most crucial determinant. UpG and CpA dinucleotides were found to be highly preferred whereas, CpG dinucleotide was mostly avoided in SARS-CoV-2, a pattern consistent with the human host. Strict avoidance of the CpG dinucleotide might be attributed to a strategy for evading a human immune response. A lower degree of adaptation of SARS-CoV-2 to the human host, compared to Middle East respiratory syndrome (MERS) coronavirus and SARS-CoV, might be indicative of its milder clinical severity and progression contrasted to SARS and MERS. Similar patterns of enhanced adaptation between viral isolates from intermediate and human hosts, contrasted with those isolated from the natural bat reservoir, signifies an indispensable role of the intermediate host in transmission dynamics and spillover events of the virus to human populations. The information regarding avoided codon pairs in SARS-CoV-2, as conferred by the present analysis, promises to be useful for the design of vaccines employing codon pair deoptimization based synthetic attenuated virus engineering.
新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已在全球迅速传播，并引起了全球的严重关注。本研究旨在对SARS-CoV-2进行全面的碱基组成分析，以揭示其对人类宿主的适应性复杂性。多变量统计分析揭示了各种因素之间的复杂相互作用，包括组成限制、自然选择、病毒编码序列的长度、病毒基因产物的亲水性和芳香性，这些因素对密码子使用模式起作用，其中组成偏好是最关键的决定因素。发现UpG和CpA二核苷酸在SARS-CoV-2中是高度优选的，而CpG二核苷酸大多被避免，这一模式与人类宿主一致。严格避免CpG二核苷酸可能归因于逃避人类免疫反应的一种策略。与中东呼吸综合征（MERS）冠状病毒和SARS-CoV相比，SARS-CoV-2对人类宿主的适应程度较低，这可能表明其临床严重程度和进展比SARS和MERS更为温和。中间宿主和人类宿主的病毒分离株之间增强适应的类似模式，与从天然蝙蝠宿主分离的病毒分离株形成对比，这表明中间宿主在病毒向人类群体的传播动态和溢出事件中起着不可或缺的作用。本分析所提供的关于SARS-CoV-2中避免的密码子对的信息，有望对采用基于密码子对去优化的合成减毒病毒工程设计疫苗有用。
