Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase

Jingyue Ju; Xiaoxu Li; Shiv Kumar; Steffen Jockusch; Minchen Chien; Chuanjuan Tao; Irina Morozova; Sergey Kalachikov; Robert N. Kirchdoerfer; James J. Russo

One factor that has confounded the development of RdRp inhibitors in coronaviruses is the presence of a 3'exonuclease-based proofreading activity such as that associated with nsp14, a key component of the replication-transcription complex in SARS-CoV, 43, 44 and also encoded in SARS-CoV-2. This exonuclease activity can be overcome with the use of 2'-O-methylated nucleotides. 43 Importantly, since both Sofosbuvir . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.12.989186 doi: bioRxiv preprint and AZT are FDA approved drugs, where toxicity tests have already been performed, they can be evaluated quickly in laboratory and clinical settings.