Antiviral compounds targeting cellular metabolism are part of the therapeutic arsenal to control the spread of
virus infection, either as sole treatment or in combination with direct-acting
antivirals (DAA) or
vaccines. Here, we describe the effect of two of them,
lauryl gallate (LG) and
valproic acid (VPA) both exhibiting a wide
antiviral spectrum, against
infection by coronaviruses such as HCoV-229E, HCoV-OC43, and SARS-CoV-2. A consistent 2 to 4-log-decrease in virus yields was observed in the presence of each
antiviral, with an average IC50 value of 1.6 μM for LG and 7.2 mM for VPA. Similar levels of inhibition were observed when adding the
drug 1 h before adsorption, at the time of
infection or 2 h after
infection, supporting a postvirus entry mechanism of action. The specificity of the
antiviral effect of LG against SARS-CoV-2, relative to other related compounds such as
gallic acid (G) and
epicatechin gallate (ECG), predicted to be better inhibitors according to in silico studies, was also demonstrated. The combined addition of LG, VPA, and
remdesivir (RDV), a DAA with a proven effect against human coronaviruses, resulted in a robust synergistic effect between LG and VPA, and to a lesser extent between the other
drug combinations. These findings reinforce the interest of these wide
antiviral spectrum host-targeted compounds as a first line of defense against
viral diseases or as a
vaccine complement to minimize the gap in antibody-mediated protection evoked by
vaccines, either in the case of SARS-CoV-2 or for other possible emerging viruses.