In Silico Prediction and Selection of Target Sequences in the SARS-CoV-2 RNA Genome for an Antiviral Attack

The SARS-CoV-2 pandemic has urged the development of protective vaccines and the search for specific antiviral drugs. The modern molecular biology tools provides alternative methods, such as CRISPR-Cas and RNA interference, that can be adapted as antiviral approaches, and contribute to this search....

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Bibliographic Details
Published in:Viruses 2022-02, Vol.14 (2), p.385
Main Authors: Hussein, Mouraya, Andrade Dos Ramos, Zaria, Berkhout, Ben, Herrera-Carrillo, Elena
Format: Article
Language:English
Subjects:
Antiviral agents
Computer Simulation
Conserved sequence
Coronaviridae
Coronaviruses
COVID-19
CRISPR
CRISPR-Cas Systems
CRISPR-Cas13d
Design
Disease transmission
Drug development
FDA approval
Gene expression
Genome, Viral
Genomes
Humans
Middle East respiratory syndrome
Nucleotide sequence
Pandemics
Pathogens
Pneumonia
Proteins
RNA, Viral - genetics
RNA-mediated interference
SARS-CoV-2 - genetics
SARS-CoV-2 genome
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - genetics
Viruses
Zoonoses
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Summary:The SARS-CoV-2 pandemic has urged the development of protective vaccines and the search for specific antiviral drugs. The modern molecular biology tools provides alternative methods, such as CRISPR-Cas and RNA interference, that can be adapted as antiviral approaches, and contribute to this search. The unique CRISPR-Cas13d system, with the small crRNA guide molecule, mediates a sequence-specific attack on RNA, and can be developed as an anti-coronavirus strategy. We analyzed the SARS-CoV-2 genome to localize the hypothetically best crRNA-annealing sites of 23 nucleotides based on our extensive expertise with sequence-specific antiviral strategies. We considered target sites of which the sequence is well-conserved among SARS-CoV-2 isolates. As we should prepare for a potential future outbreak of related viruses, we screened for targets that are conserved between SARS-CoV-2 and SARS-CoV. To further broaden the search, we screened for targets that are conserved between SARS-CoV-2 and the more distantly related MERS-CoV, as well as the four other human coronaviruses (OC43, 229E, NL63, HKU1). Finally, we performed a search for pan-corona target sequences that are conserved among all these coronaviruses, including the new Omicron variant, that are able to replicate in humans. This survey may contribute to the design of effective, safe, and escape-proof antiviral strategies to prepare for future pandemics.
ISSN:1999-4915
1999-4915
DOI:10.3390/v14020385