In Silico Screening of Phytoconstituents from Hypericum sp. as JAK3 Inhibitors for Autoimmune Disorders

Abstract

Janus kinase (JAK)s has become a viable therapeutic target, for autoimmune and inflammatory diseases. However, its use is complicated by over 50 different cytokines involved in immune responses, potentially leading to adverse consequences. Among JAKs JAK3 has substantial immunomodulatory effects. Indeed, JAK3 emerges as an exceptionally appealing target for therapeutic interventions in autoimmune and inflammatory disorders. Therefore, it is critical to develop specific JAK3 inhibitors. The present investigation utilized Pyrx and to conduct virtual screening and molecular docking analysis on the active components from one of the species of Hypericum i.e. Hypericum perforatum, with the JAK3 receptor. Among the phytoconstituents hypericin, demonstrated an exceptional affinity (-12.4 kcal/mol) for the JAK3 protein. Additionally, hypericin exhibited favorable ADMET properties as predicted by pkCSM and Swiss ADME, supporting its potential as a drug candidate. The findings suggest that hypericin might serve as a viable therapeutic alternative for autoimmune disorders. However, in vivo and in vitro investigations specific to JAK3 are required to validate and extend these results.