Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames; David Dillon Holcomb; Ofer Kimchi; Michael DiCuccio; Nobuko Hamasaki-Katagiri; Tony Wang; Anton A Komar; Aikaterini Alexaki; Chava Kimchi-Sarfaty

We have conducted a thorough analysis of the codon, codon pair and dinucleotide usage of the SARS-CoV-2 and have assessed how it relates to other coronaviruses, its hosts, and to the tissues that SARS-CoV-2 has been reported to infect [21] [22] [23] . We have taken advantage of our recently published databases, which include genomic codon usage statistics for all species with available sequence data, and transcriptomic codon usage statistics from several human tissues [4, 5, 24] . We further analyzed each viral gene in terms of its codon characteristics and used an array of codon usage metrics that informed us of the potential of each gene sequence to contribute to the deoptimization of the virus. In the case of ORF1ab, we further examined the structure of the mRNA in the region following the frameshift, finding the SARS-CoV-2 mRNA to exhibit a similar pseudoknotted structure to known coronaviruses. We identified two viral genes that represent valuable targets for deoptimization to generate an attenuated virus. Our analysis can be used as a pipeline to guide codon pair deoptimization for viral attenuation and vaccine development or a posteriori to evaluate the effectiveness of an attenuated viral sequence.