Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2.

Karayiannis, P.; Thursz, M.; Sadiq, F.; Tree, J.; Beasley, D.; Dejnirattisai, W.; Mongkolsapaya, J.; Screaton, G.; Wand, M.; Elmore, M.; Miles, C.; Matthews, I.; Thomas, H.

doi:10.1101/2022.09.23.509178

bioRxiv · 10.1101/2022.09.23.509178

Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2.

Karayiannis, P.·Thursz, M.·Sadiq, F.·Tree, J.·Beasley, D.·Dejnirattisai, W.·Mongkolsapaya, J.·Screaton, G.·Wand, M.·Elmore, M.·Miles, C.·Matthews, I.·Thomas, H.

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Abstract

Phosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and inhibit, both in vitro and in vivo, the replication of several RNA viruses including hepatitis C virus (HCV), dengue virus (DENV), West Nile Virus (WNV) and SARS-CoV-2.

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Karayiannis, P., Thursz, M., Sadiq, F., Tree, J., Beasley, D., Dejnirattisai, W., Mongkolsapaya, J., Screaton, G., Wand, M., Elmore, M., Miles, C., Matthews, I., Thomas, H.. 2022-09-26. Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2.. https://doi.org/10.1101/2022.09.23.509178

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