PMC:7600245 / 26472-27992 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7600245","sourcedb":"PMC","sourceid":"7600245","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7600245","text":"It is the isopropyl-ester prodrug of β-D-N4-hydroxycytidine (Figure 5A). The prodrug has improved oral bioavailability as it avoids phosphorylation of the N4-hydroxyl group in the gastrointestinal tract. It is hydrolyzed in vivo to release the parent (EIDD-1931), which distributes into tissues, and upon tri-phosphorylation, it becomes the active triphosphate form. The tri-phosphorylated form has a broad-spectrum antiviral activity against various RNA viruses, including influenza, Ebola, Venezuelan equine encephalitis virus, MERS-CoV, SARS-CoV, SARS-CoV-2 and related zoonotic group 2b or 2c bat coronaviruses [80,81]. It also demonstrated increased potency against a coronavirus with resistance mutations to remdesivir [82]. By the action of RdRp, the active form is incorporated into the genome of RNA viruses, leading to the accumulation of mutations known as viral error catastrophe [80]. The active form exists in two forms (Figure 5B): the oxime form which mimics uridine and pairs with adenosine, while the other tautomer mimics cytidine and pairs with guanosine [81]. In mice infected with MERS-CoV or SARS-CoV, EIDD-2801 administration was found to diminish the virus titer and body weight loss and to improve pulmonary function [80]. Reduced MERS-CoV yields in vitro and in vivo was because of the increase in transition mutation frequency in only the viral RNA. The drug produced similar results in human airway epithelial cells. The drug showed similar results as a prophylactic and as a treatment 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