In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 5 ( 2022-5-19), p. e1010498-
Abstract:
Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC 50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a post-entry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010498
DOI:
10.1371/journal.ppat.1010498.g001
DOI:
10.1371/journal.ppat.1010498.g002
DOI:
10.1371/journal.ppat.1010498.g003
DOI:
10.1371/journal.ppat.1010498.g004
DOI:
10.1371/journal.ppat.1010498.g005
DOI:
10.1371/journal.ppat.1010498.s001
DOI:
10.1371/journal.ppat.1010498.s002
DOI:
10.1371/journal.ppat.1010498.s003
DOI:
10.1371/journal.ppat.1010498.s004
DOI:
10.1371/journal.ppat.1010498.s005
DOI:
10.1371/journal.ppat.1010498.s006
DOI:
10.1371/journal.ppat.1010498.s007
DOI:
10.1371/journal.ppat.1010498.s008
DOI:
10.1371/journal.ppat.1010498.r001
DOI:
10.1371/journal.ppat.1010498.r002
DOI:
10.1371/journal.ppat.1010498.r003
DOI:
10.1371/journal.ppat.1010498.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
Permalink