The unprecedent situation generated by the COVID-19 global emergency has prompted scientists around the world to actively work to fight against this pandemic. In this sense, it is remarkable the number of drug repurposing efforts trying to shed light into the COVID-19 patients treatment. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. A successful combination of a multi-target virtual screening approach focused on host-based targets related to viral entry and experimental evaluation of the antiviral activity of selected compounds has been carried out. As a result, three different potentially repurposable drugs interfering with viral entry, cepharantine, imatinib and efloxate, have been identified.

Funding from CSIC (201980E024, 202020E103 and PIE-RD-COVID-19 ref. E202020E079), EVA (European Virus Archive; grant agreement No 871029), FONDECYT grant Nº 11180604 and CONICYT-PCI grant Nº REDES190074 is acknowledged. Dr. R. Molenkamp (Erasmus University Medical Center, Rotterdam, Netherlands; participant of the EVA-GLOBAL project) is acknowledged for the SARS32 CoV-2 strain NL/2020 virus. Dr. F. L. (Inserm-Lyon) is acknowledged for the materials required to produce retroviral pseudotypes

Peer reviewed