What is it about?

We use a new methodology to show the presence of short persistent DNA/RNA sequences in SARS-CoV-2 that are absent from the human genome and transcriptome. Among these sequences, one is of particular interest since it occurs in the Spike glycoprotein coding sequence. This viral protein is fundamental for infection and proliferation of the virus in the human body since it plays a crucial role in binding to the human Angiotensin-converting enzyme 2 (ACE2), an enzyme attached to the human cell membranes of cells in the lungs, arteries, heart, kidney, and intestines. As such, this protein is used as an entry receptor to invade target cells. By applying protein structural prediction, we localized that these short persistent DNA/RNA sequences of SARS-CoV-2 occur in the Spike protein surface, providing a potential targeted vector for diagnostics and therapeutics.

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Why is it important?

These sequences are persistent, meaning they occur across all the SARS-CoV-2 genomes studied in the paper. Furthermore, these are small sequences (12-13 nucleotides), making these regions more robust to mutation. This is relevant in viral testing and treatment since viruses are highly mutable. Furthermore, all the persistent sequences fall in regions without mutations, including SNPs. Additionally, all the mRAWs do not fall in the redundant areas that are usually associated with loops, copies, or poly-A tails. These Persistent minimal sequences can be used in diagnosis to design primers that identify SARS-CoV-2 infections or distinguish between coronavirus species, improving testing sensitivity. The evolution of SARS-CoV-2 is supplied by replicating RNA sequences with mutations, mainly SNPs, harming the RT-PCR method’s sensitivity. Identifying persistent minimal sequences in SARS-CoV-2 allows for enhancing the RT-PCR methodologies by using conserved regions between multiple genomes of SARS-CoV-2. The reported PmRAWs are absent from other human coronaviruses and diminish the probability of cross-reaction. Moreover, identifying persistent sequences absent from the human genome and transcriptome permits isolating the SARS-CoV-2 signal from possible human material that abounds in the cell in higher magnitude orders of quantity. The identified Persistent minimal sequence found in the Spike glycoprotein coding sequence may be a key for a potential target therapeutic, given its singularity, persistency, and exposure at the Spike protein surface. The SARS-Cov-2 Spike (S) glycoprotein is being used as a target for vaccines because Spike binds into the angiotensin-converting enzyme (ACE) 2 human receptor for a further injection of the viral mRNA into the human cell. The methodology can be applied to any viral sequence. In the future, this can be used to create more efficient tests and treatments for other types of viral infections.

Perspectives

Besides being highly relevant in creating new tests and treatments for covid, this is a straightforward approach that can be applied to any viral sequence to produce more efficient tests and treatments for other viral infections.

Dr. Jorge Miguel Silva
Universidade de Aveiro

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This page is a summary of: Persistent minimal sequences of SARS-CoV-2, Bioinformatics, July 2020, Oxford University Press (OUP),
DOI: 10.1093/bioinformatics/btaa686.
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