Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/344694
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Title

Inhibition of Human Coronaviruses by Combinations of Host-Targeted and Direct-Acting Antivirals

AuthorsLeón, Patricia de CSIC ORCID; Cañas-Arranz, Rodrigo; Bustos, Maria José CSIC ORCID; Sáiz, Margarita CSIC ORCID; Sobrino Castelló, Francisco CSIC ORCID
KeywordsCoronavirus
SARS-CoV-2
Host-targeted antivirals
Direct-acting antivirals
Lauryl gallate
Valproic acid
Remdesivir
Synergy
Issue DateApr-2023
PublisherAmerican Society for Microbiology
CitationAntimicrobial Agents and Chemotherapy 67(4): e01703-22 (2023)
AbstractAntiviral 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.
URIhttp://hdl.handle.net/10261/344694
DOI10.1128/aac.01703-22
ISSN0066-4804
E-ISSN1098-6596
Appears in Collections:(CBM) Artículos
(PTI Salud Global) Colección Especial COVID-19




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