TABLE 1.
In vitro activity of AT-511 and other oral antiviral drugs against various human coronavirusesa
Virus (genus) | Cell line | Compound | CPE assay |
VYR assay EC90 (μM [n]) | Selectivity index (CC50/EC50) | |
---|---|---|---|---|---|---|
EC50 (μM [n]) | CC50 (μM) | |||||
HCoV-229E (Alphacoronavirus) | BHK-21 | AT-511 | 1.8 ± 0.3 [2] | >100 | ND | >55 |
BHK-21 | Sofosbuvir | >100 | >100 | ND | ND | |
Huh-7 | AT-511 | 1.7 ± 0.1 [2] | >86 | 1.2 ± 0.1 [2] | >50 | |
HCoV-OC43 (Betacoronavirus) | Huh-7 | AT-511 | NDb | >86 | 0.5 | >170c |
RD | AT-511 | 2.8 | >86 | 2.2 | >30 | |
MERS-CoV (Betacoronavirus) | Huh-7 | AT-511 | 26 ± 15 [2] | >86 | 37 ± 28 [2] | >3.3 |
SARS-CoV (Betacoronavirus) | Huh-7 | AT-511 | NDb | >86 | 0.34 | >250c |
SARS-CoV-2 (Betacoronavirus) | HAE | AT-511 | NDb | >86d | 0.47 ± 0.12 [5] | >160c |
HAE | Molnupiravir | NDb | >19d | 2.8 ± 1.0 [3] | >4.9c |
The activity of AT-511 and other antiviral compounds was measured in cells infected with different coronaviruses, using the cytopathic effect (neutral red dye) assay and/or the virus yield reduction (VYR) assay as described in Materials and Methods, to determine the effective concentration required to achieve 50% inhibition (EC50) of the virus-induced cytopathic effect (CPE), the concentration to reduce virus yield by 1 log10 (EC90), and the cytotoxic concentration of the drug to cause death to 50% of viable cells without virus (CC50). Values represent results from single or multiple (mean ± SD [n]) experiments.
Not determined because no cytopathic effect was produced by this virus in this cell line.
CC50/EC90, since EC50 could not be determined by measuring CPE in the neutral red assay.
Cytotoxicity assessed by visual inspection of cell monolayers.