The Food and Drug Administration-approved antipsychotic drug trifluoperazine, a calmodulin antagonist, inhibits viral replication through PERK-eIF2α axis.

ABSTRACT: Virus-related diseases are seriously threatening human health, but there are currently only 10 viruses with clinically approved antiviral drugs available. As non-cellular organisms, viruses parasitize in living cells and rely on the protein synthesis mechanism of the host cells. In this study, we found that the antipsychotic drug trifluoperazine (TFP), a dual dopamine receptor D2 (DRD2)/calmodulin (CALM) antagonist, increases the phosphorylation of eukaryotic initiation factor 2α (eIF2α), a key factor in the regulation of protein synthesis and significantly inhibits vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) replication. CALM but not DRD2 is involved in the antiviral activity of TFP. By knockdown of protein kinase R (PKR)-like endoplasmic reticulum kinase (PER

SUBMITTER: Mao Y 

PROVIDER: S-EPMC9664084 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature