The ongoing SARS-CoV-2 pandemic has caused more than 500,000 infections and more than 25,000 deaths in 199 countries. All human CoV are thought to have emerged originally as zoonoses ( 4– 6). Three new human CoV have emerged in the past 20 years with severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012, and now SARS-CoV-2 in 2019 ( 1– 3). Phylogenetically, CoVs are divided into four genera: alpha (group 1), beta (group 2), gamma (group 3), and delta (group 4). The genetically diverse Orthocoronavirinae family circulates in many avian and mammalian species. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral, but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC prodrug (β- d-N 4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Here, we show that the ribonucleoside analog β- d-N 4-hydroxycytidine (NHC EIDD-1931) has broad-spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c bat-CoVs, as well as increased potency against a CoV bearing resistance mutations to the nucleoside analog inhibitor remdesivir.
![fx chem labs fx chem labs](https://rcscenedeutschland.files.wordpress.com/2021/03/fx-chem-labs.png)
Baric Show FewerĬoronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Kolykhalov, George Painter, Jennifer Harcourt, Azaibi Tamin, Natalie J. Natchus, Manohar Saindane, Alexander A. Leist, … Show All …, Alexandra Schäfer, Kenneth H.