RT Journal Article
SR Electronic
T1 Nucleotide Analogues as Inhibitors of Viral Polymerases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.30.927574
DO 10.1101/2020.01.30.927574
A1 Jingyue Ju
A1 Shiv Kumar
A1 Xiaoxu Li
A1 Steffen Jockusch
A1 James J. Russo
YR 2020
UL http://biorxiv.org/content/early/2020/01/31/2020.01.30.927574.abstract
AB 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.