Antiviral error catastrophe

Abstract

Coronavirus The development of broadspectrum antiviral drugs is desirable, particularly in the context of emerging zoonotic infections for which specific interventions do not yet exist. Sheahan et al. tested the potential of a ribonucleoside analog, β-d-N4-hydroxycytidine, which was previously shown to be active against RNA viruses such as influenza and Ebola virus, to inhibit coronaviruses. This drug was effective in cell lines and primary human airway epithelial cultures against multiple coronaviruses, including severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Mouse models of two other coronaviruses demonstrated that early treatment reduced viral replication and damage to the lungs. Mechanistically, this drug is incorporated into the viral RNA, inducing mutations and eventually leading to error catastrophe in the virus. Sci. Transl. Med. 12 , eabb5883 (2020).