A Synthetic Biology Approach for Vaccine Candidate Design against Delta Strain of SARS-CoV-2 Revealed Disruption of Favored Codon Pair as a Better Strategy over Using Rare Codons

Pankaj Gurjar; Noushad Karuvantevida; Igor Vladimirovich Rzhepakovsky; Azmat Ali Khan; Rekha Khandia

doi:10.3390/vaccines11020487

A Synthetic Biology Approach for Vaccine Candidate Design against Delta Strain of SARS-CoV-2 Revealed Disruption of Favored Codon Pair as a Better Strategy over Using Rare Codons

Vaccines (Basel). 2023 Feb 20;11(2):487. doi: 10.3390/vaccines11020487.

Authors

Pankaj Gurjar¹, Noushad Karuvantevida², Igor Vladimirovich Rzhepakovsky³, Azmat Ali Khan⁴, Rekha Khandia⁵

Affiliations

¹ Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia.
² College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates.
³ Medical and Biological Faculty, North Caucasus Federal University, 355017 Stavropol, Russia.
⁴ Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁵ Department of Biochemistry and Genetics, Barkatullah Universty, Bhopal 462026, India.

Abstract

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.

Keywords: SARS-CoV-2 delta vaccine candidate; codon context; codon optimization; codon pair; rare codon; synthetic biology.

Grants and funding

This work was funded by the Researchers Supporting Project Number (RSP2023R339) King Saud University, Riyadh, Saudi Arabia.