Structure-Altering Mutations of the SARS-CoV-2 Frame Shifting RNA Element.

BioRxiv : the Preprint Server for Biology
Tamar SchlickShuting Yan

Abstract

With the rapid rate of Covid-19 infections and deaths, treatments and cures besides hand washing, social distancing, masks, isolation, and quarantines are urgently needed. The treatments and vaccines rely on the basic biophysics of the complex viral apparatus. While proteins are serving as main drug and vaccine targets, therapeutic approaches targeting the 30,000 nucleotide RNA viral genome form important complementary approaches. Indeed, the high conservation of the viral genome, its close evolutionary relationship to other viruses, and the rise of gene editing and RNA-based vaccines all argue for a focus on the RNA agent itself. One of the key steps in the viral replication cycle inside host cells is the ribosomal frameshifting required for translation of overlapping open reading frames. The frameshifting element (FSE), one of three highly conserved regions of coronaviruses, includes an RNA pseudoknot considered essential for this ribosomal switching. In this work, we apply our graph-theory-based framework for representing RNA secondary structures, "RAG" (RNA-As Graphs), to alter key structural features of the FSE of the SARS-CoV-2 virus. Specifically, using RAG machinery of genetic algorithms for inverse folding adapted for ...Continue Reading

Citations

Feb 9, 2021·Emergent Materials·Abhimanyu TharayilNandakumar Kalarikkal

Datasets Mentioned

BETA
MT246482

Methods Mentioned

BETA
PCA
SHAPE-MaP

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