Antiviral activity of pimecrolimus against dengue virus type 2 infection in vitro and in vivo

• Published in: Scientific reports 2024-06, Vol.14 (1), p.13303-11
• Main Authors: Kim, Seong-Ryeol, Lee, Jung-Min, Kang, Hae Ji, Ryou, Jungsang, Shim, Sang-Mu
• Format: Article
• Language: English
• Subjects: 631/326/596/1413; 692/308/153; Aedes; Animals; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Aquatic insects; Body weight; Body weight loss; Cell death; Cell Line; Chlorocebus aethiops; Dengue - drug therapy; Dengue - virology; Dengue fever; Dengue hemorrhagic fever; Dengue Virus - drug effects; Disease Models, Animal; Disease transmission; Drug development; Env protein; Humanities and Social Sciences; Humans; Infections; Lethality; Mice; Mosquitoes; multidisciplinary; Oral administration; Public health; Replication; Science; Science (multidisciplinary); Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology; Tacrolimus - therapeutic use; Vector-borne diseases; Vero Cells; Viral envelope proteins; Virus Replication - drug effects; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-61127-x

Dengue virus (DENV) infection is a public health concern in several countries and is associated with severe diseases, such as dengue hemorrhagic fever and dengue shock syndrome. DENVs are transmitted to humans via the bites of infected Aedes mosquitoes, and no antiviral therapeutics are currently available. In this work, we aimed to identify antiviral drugs against DENV type 2 (DENV2) infections and selected pimecrolimus as a potential antiviral drug candidate. Pimecrolimus significantly inhibited DENV2-mediated cell death and replication in vitro. We also confirmed a decrease in the number of plaques formed as well as in the envelope protein levels of DENV2. The time-of-addition and course experiments revealed that pimecrolimus inhibited DENV2 infection during the early stages of the virus replication cycle. In an experimental mouse model, orally administered pimecrolimus alleviated body weight loss and lethality caused by DENV2 infection, which we used as readouts of the drug’s antiviral potency. Furthermore, pimecrolimus significantly inhibited the DENV2 load and ameliorated focal necrosis in the liver and spleen. Taken together, our in vitro and in vivo findings suggest that pimecrolimus is a promising antiviral drug candidate for the treatment of DENV2 infection.