Prediction of the Effects of Synonymous Variants on SARS-CoV-2 Genome

Abstract

Background:\xa0The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\xa0had led to\xa0a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which\xa0mutates at a higher rate. Multiple studies had been done to identify\xa0and study\xa0nonsynonymous mutations, which change amino acid residues of\xa0SARS-CoV-2\xa0proteins.\xa0On the other hand,\xa0there is\xa0little\xa0study\xa0on\xa0the effects of\xa0SARS-CoV-2\xa0synonymous mutations.\xa0Although these mutations\xa0do not alter amino acids,\xa0some studies suggest\xa0that\xa0they\xa0may affect viral fitness.\xa0This study\xa0aims\xa0to predict\xa0the effect of\xa0synonymous mutations\xa0on\xa0the\xa0SARS-CoV-2\xa0genome.\xa0\xa0 Methods:\xa0A total of 30,229 SARS-CoV-2 genomic sequences were retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database\xa0and aligned using MAFFT.\xa0Then, the mutations and their respective frequency were identified.\xa0A prediction of\xa0RNA secondary structures and their base pair probabilities was\xa0performed\xa0to\xa0study the effect of synonymous mutations on RNA\xa0structure and stability.\xa0Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2.\xa0 Results:\xa0A\xa0total of 150 synonymous mutations were identified.\xa0The synonymous mutation identified with the highest frequency is C3037U\xa0mutation in the nsp3 of ORF1a, followed by C313U\xa0and C9286U\xa0mutation in nsp1 and nsp4 of ORF1a, respectively.\xa0\xa0 Conclusion:\xa0Among\xa0the\xa0synonymous mutations identified, C913U\xa0mutation in ORF1a and C26735U\xa0in membrane (M) protein\xa0may\xa0affect\xa0RNA\xa0secondary structure, reducing the stability of\xa0RNA\xa0folding\xa0and\xa0possibly\xa0resulting in\xa0a higher translation rate.\xa0However, lab experiments are required to\xa0validate the\xa0results obtained from prediction\xa0analysis.