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bioRxiv · 10.1101/2022.03.04.483076

Crippled Coronavirus: 5'-PolyU targeted Oligo prevents development of infectious Virions

Ullah, H.·Averick, S.·Tang, Q.
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Abstract

Current RNA viral pandemic of COVID-19 has been worsened by rapidly spreading viral variants. To inhibit mutation-based development of new escape variants, elements that are indispensable for the virus may be targeted. The 5-polyU tract of the antigenome offers one such target. Host cells do not harbor 5-polyU tracts on any of their transcripts, making the tract an attractive virus-specific target. We hypothesize that inhibiting the 5-polyU by complementary oligonucleotide can limit the use of the tract as template for virus to generate 3 polyA tails of RNA viruses. Here, we used a frameshift-inducing DNA oligonucleotide with 3 polyAs to target the 5-polyU tract of mouse coronavirus (MHV-A59). Results from assays for double stranded RNA (dsRNA) synthesis, infectivity of released virions, and syncytium formation indicate that the oligonucleotide treatment prevented generation of infectious virions. Our results show a unique mode of action of the designed 3-polyA oligonucleotide against mouse coronavirus which leaves host cells unaffected. This strategy can be adopted for the development of novel classes of oligonucleotide-based drugs that inhibit the production of infectious RNA viruses, including the coronaviruses. Since the 5-polyU tract is conserved and is essential for variants of coronaviruses, this strategy can potentially address coronavirus variant emergence as well.

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Ullah, H., Averick, S., Tang, Q.. 2022-03-07. Crippled Coronavirus: 5'-PolyU targeted Oligo prevents development of infectious Virions. https://doi.org/10.1101/2022.03.04.483076

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