Repurposing existing antiviral drugs is a key strategy in our efforts to develop effective therapies to tackle the consequences of COVID-19. Many recent studies have investigated the impact of psychoactive drugs on SARS-CoV-2 in cell culture and on clinical practice. Researchers from Finland have expanded on these studies and tested some of the approved psychoactive drugs against the new SARS-CoV-2 variants.
The results of this study are published on a preprint server. The team chose several antidepressant and antipsychotic drugs with different primary modes of action and tested them against SARS-CoV-2 spike protein-dependent infection by pseudoviruses in human embryonic kidney cells expressing ACE2/TMPRSS2. Some of these molecules were also tested against the B.1 lineage of SARS-CoV-2 and the newer variants, B.1.1.7 and B.1.351, in Calu-1, a human lung epithelial cell line. Several clinically prescribed antidepressants, including citalopram, fluoxetine, imipramine, and reboxetine, as well as antipsychotic compounds such as flupenthixol, chlorpromazine, and pimozide, were found to be capable of inhibiting infection by pseudoviruses with minimal impact on cell viability. The antiviral activity of many of these drugs was tested in Calu-1 cells against the B.1 SARS-CoV-2 lineage.
In contrast, in the pseudovirus model, the anticonvulsant carbamazepine, and antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity. Moreover, fluoxetine was effective against pseudoviruses with the K417N, N501Y, and E484K spike mutations, and the SARS-CoV-2 variants – VoC-1 (B.1.1.7) and VoC-2 (B.1.351).
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