Nucleotide Analogues as Inhibitors of Viral Polymerases

Ju, J.; Kumar, S.; Li, X.; Jockusch, S.; Russo, J. J.

doi:10.1101/2020.01.30.927574

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bioRxiv · 10.1101/2020.01.30.927574

Nucleotide Analogues as Inhibitors of Viral Polymerases

Ju, J.·Kumar, S.·Li, X.·Jockusch, S.·Russo, J. J.

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Abstract

Coronaviruses such as the newly discovered virus from Wuhan, China, 2019-nCoV, and the viruses that cause SARS and MERS, have resulted in regional and global public health emergencies. Based on our molecular insight that the hepatitis C virus and the coronavirus use a similar viral genome replication mechanism, we reasoned that the FDA-approved drug EPCLUSA (Sofosbuvir/Velpatasvir) for the treatment of hepatitis C will also inhibit the above coronaviruses, including 2019-nCoV. To develop broad spectrum anti-viral agents, we further describe a novel strategy to design and synthesize viral polymerase inhibitors, by combining the ProTide Prodrug approach used in the development of Sofosbuvir with the use of 3-blocking groups that we have previously built into nucleotide analogues that function as polymerase terminators.

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Ju, J., Kumar, S., Li, X., Jockusch, S., Russo, J. J.. 2020-01-31. Nucleotide Analogues as Inhibitors of Viral Polymerases. https://doi.org/10.1101/2020.01.30.927574

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