Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 477, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2023.116695
Keywords
Paxlovid; Synthetic cytotoxicity; Liver toxicity; Drug combinations; Small molecule drugs
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This study aimed to investigate the synthetic cytotoxicity interaction between Paxlovid and 100 frequently used small molecule drugs and further explore the structural modulation through molecular docking simulation with Caspase-8.
Paxlovid is a recent FDA approved specific drug for COVID-19. Extensive prescription of Paxlovid could induce potential synthetic cytotoxicity with drugs. Herein, we aimed to examine pairwise synthetic cytotoxicity between Paxlovid and 100 frequently FDA approved small molecule drugs. Liver cell line HL-7702 or L02 was adopted to evaluate synthetic cytotoxicity between Paxlovid and the 100 small molecule drugs. Inhibitory concentration IC10 and IC-50 doses for all the 100 small molecule drugs and Paxlovid were experimentally acquired. Then, pairwise synthetic cytotoxicity was examined with the fixed dose IC-10 for each drug. The most 4 significant interactive pairs (2 positively interactive and 2 negatively interactive) were further subjected to molecular docking simulation to reveal the structural modulation with Caspase-8, a key mediator for cell apoptosis.
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