In vitro and in vivo efficacy of a multi-component drug containing GS-441524 against feline coronavirus and SARS-CoV-2

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide public health concern despite available vaccines. In cats another relevant coronavirus the feline Coronavirus (FCoV) causes the deadly disease feline infectious peritonitis (FIP). GS-441524, the metabolite of remdesivir, is effective against SARS-CoV-2 in a mouse model, and has been used successfully to treat cats with FIP. The excellent efficacy of a multi-component drug Xraphconn® containing GS-441524 was demonstrated recently by curing cats with FIP. The aim of this study was to evaluate the antiviral efficacy of Xraphconn® compared to pure GS-441524 in vitro against both FCoV and SARS-CoV-2 as well as in vivo against SARS-CoV-2. Xraphconn® inhibited the viral replication of SARS-CoV-2 and FCoV at non-cytotoxic concentrations. Moreover, even a lower concentration of MTX inhibits the virus growth of SARS-CoV-2 compared to GS-441254. In vivo efficacy of Xraphconn® against SARS-CoV-2 was investigated in orally or intraperitoneally treated K18-hACE-2 mice. Unfortunately, SARS-CoV-2 caused a severe and lethal infection in K18-hACE-2 mice. No in vivo antiviral effects could be demonstrated. Thus, further studies in a SARS-CoV-2 suitable infection model are needed to assess impact of administration route, relationship between efficacy and timing of drug administration and role of additional active ingredients aside from GS-441524 in the multi-component drug Xraphconn®