Gurjar Pankaj, Karuvantevida Noushad, Rzhepakovsky Igor Vladimirovich, Khan Azmat Ali, Khandia Rekha
Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia.
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates.
Vaccines (Basel). 2023 Feb 20;11(2):487. doi: 10.3390/vaccines11020487.
The SARS-CoV-2 delta variant (B.1.617.2) appeared for the first time in December 2020 and later spread worldwide. Currently available vaccines are not so efficacious in curbing the viral pathogenesis of the delta strain of COVID; therefore, the development of a safe and effective vaccine is required. In the present study, we envisaged molecular patterns in the structural genes' spike, nucleoprotein, membrane, and envelope of the SARS-CoV-2 delta variant. The study was based on determining compositional features, dinucleotide odds ratio, synonymous codon usage, positive and negative codon contexts, rare codons, and insight into relatedness between the human host isoacceptor tRNA and preferred codons from the structural genes. We found specific patterns, including a significant abundance of T nucleotide over all other three nucleotides. The underrepresentation of GpA, GpG, CpC, and CpG dinucleotides and the overrepresentation of TpT, ApA, CpT, and TpG were observed. A preference towards ACT- (Thr), AAT- (Asn), TTT- (Phe), and TTG- (Leu) initiated codons and aversion towards CGG (Arg), CCG (Pro), and CAC (His) was present in the structural genes of the delta strain. The interaction between the host tRNA pool and preferred codons of the envisaged structural genes revealed that the virus preferred the codons for those suboptimal numbers of isoacceptor tRNA were present. We see this as a strategy adapted by the virus to keep the translation rate low to facilitate the correct folding of viral proteins. The information generated in the study helps design the attenuated vaccine candidate against the SARS-CoV-2 delta variant using a synthetic biology approach. Three strategies were tested: changing TpT to TpA, introducing rare codons, and disrupting favored codons. It found that disrupting favored codons is a better approach to reducing virus fitness and attenuating SARS-CoV-2 delta strain using structural genes.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）德尔塔变异株（B.1.617.2）于2020年12月首次出现，随后在全球范围内传播。目前可用的疫苗在抑制新冠病毒德尔塔毒株的病毒发病机制方面效果不佳；因此，需要研发一种安全有效的疫苗。在本研究中，我们设想了SARS-CoV-2德尔塔变异株结构基因刺突蛋白、核蛋白、膜蛋白和包膜蛋白中的分子模式。该研究基于确定组成特征、二核苷酸优势比、同义密码子使用情况、正负密码子上下文、稀有密码子，以及洞察人类宿主同功受体tRNA与结构基因中偏好密码子之间的相关性。我们发现了特定模式，包括T核苷酸在所有其他三种核苷酸中显著丰富。观察到GpA、GpG、CpC和CpG二核苷酸的代表性不足以及TpT、ApA、CpT和TpG的代表性过高。德尔塔毒株的结构基因中存在对以ACT-（苏氨酸）、AAT-（天冬酰胺）、TTT-（苯丙氨酸）和TTG-（亮氨酸）起始的密码子的偏好以及对CGG（精氨酸）、CCG（脯氨酸）和CAC（组氨酸）的厌恶。宿主tRNA库与设想的结构基因的偏好密码子之间的相互作用表明，病毒偏好那些同功受体tRNA数量次优的密码子。我们将此视为病毒采用的一种策略，以保持低翻译速率，促进病毒蛋白的正确折叠。该研究中产生的信息有助于使用合成生物学方法设计针对SARS-CoV-2德尔塔变异株的减毒候选疫苗。测试了三种策略：将TpT改为TpA、引入稀有密码子以及破坏偏好密码子。结果发现，破坏偏好密码子是一种更好的方法，可利用结构基因降低病毒适应性并减弱SARS-CoV-2德尔塔毒株。
