Anthracyclines inhibit -1 programmed ribosomal frameshifting and restrict HCoV-OC43 infection
Scheller, D.; Islam, K.; Lindgren, L.; Arnberg, N.; Johansson, J.
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Human coronavirus OC43 (HCoV-OC43) constitutes one of the most common causes of the seasonal cold but can also cause severe disease among elderly and immuno-compromised. Currently, there are no approved antiviral drugs to combat HCoV-OC43 infection. Coronaviruses are positive single-stranded RNA (+ssRNA) viruses and utilize -1 programmed ribosomal frameshifting (-1 PRF) to obtain the correct stoichiometry of viral protein components. As such, the ribosomal frameshifting stimulation element (FSE) is a promising target for antiviral drug discovery, due to its high conservation. By repurposing available drugs, we identified a group of anthracycline compounds that can reduce -1 PRF of HCoV-OC43 and reduce viral infection of cells. Furthermore, we show that anthracyclines that reduce infection also bind the FSE and reduce frameshift frequency. We also show that the selected anthracyclines reduce SARS-CoV-2 infection, but without affecting -1 PRF frequency. All together, we demonstrate that a subset of anthracyclines selectively binds and inhibit the HCoV-OC43 FSE and could thus serve as a robust framework when developing new antivirals targeting coronaviruses.
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