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MeSH Disease

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SARS-CoV-2 proteins

ORF1 (1)

ORF1a (1)

ORF1ab (1)


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    Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses

    Authors: Vladislav Victorovich Khrustalev; Rajanish Giri; Tatyana Aleksandrovna Khrustaleva; Shivani Krishna Kapuganti; Aleksander Nicolaevich Stojarov; Victor Vitoldovich Poboinev

    doi:10.1101/2020.05.05.078238 Date: 2020-05-05 Source: bioRxiv

    Within four months of the ongoing COVID-19 pandemic MESHD COVID-19 pandemic MESHD caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in the ORF1 PROTEIN of the virus isolated from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a PROTEIN and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of nonsynonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerated sites towards uracil residues is seen in ORF1 PROTEIN of all the studied coronaviruses. A more substantial mutational U pressure is observed in ORF1a PROTEIN than in ORF1b owing to the translation of ORF1ab PROTEIN via programmed ribosomal frameshifting. Unlike other nucleotide mutations, mutational U pressure caused by cytosine deamination, mostly occurring in the RNA-plus strand, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the direction of mutational pressure during translation of viral RNA-plus strands has implications for vaccine and nucleoside analogue development for treating covid-19 MESHD and other coronavirus infections MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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