EIDD-2801 is the isopropylester prodrug of the ribonucleoside analogue β-D-N4-hydroxycytidine
(EIDD-1931, or N-hydroxycytidine) [1
]. It was originally designed by Emory University chemists to inhibit replication of influenza virus. It has subsequently been tested for activity against other RNA viruses, including pandemic SARS-CoV-2, SARS-CoV and MERS-CoV [2
]. The active form of EIDD-2801 exists in two tautomeric forms, one which is a uridine mimic (pairs with adenosine), and the second which mimics cytidine (pairs with guanosine). During RNA replication switching between these tautomers causes mismatches and leads to catastrophic mutation within the new viral RNA transcripts which render it non-functional. Remdesivir
is another nucleoside analogue that is being evaluated in human trials for efficacy against SARS-CoV-2 infection. The active forms of both compounds block viral RNA-dependent RNA polymerase to prevent virus replication, but in slightly different ways, suggesting that their effects may be complementary. Another difference between remdesivir and EIDD-2801 is that while remdesivir needs to be administered intravenously within a medical setting, EIDD-2801 is orally bioavailable, so could be taken at home. This offers the potential for treatment to be initiated earlier in the course of the disease, before more severe symptoms develop.