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Antipoxvirus Activity Evaluation of Optimized Corroles Based on Development of Autofluorescent ANCHOR Myxoma Virus.

Authors :
Kappler-Gratias S
Bucher L
Top S
Quentin-Froignant C
Desbois N
Bertagnoli S
Louison M
Monge E
Bousquet-Melou A
Lacroix M
Gros CP
Gallardo F
Source :
ACS infectious diseases [ACS Infect Dis] 2021 Aug 13; Vol. 7 (8), pp. 2370-2382. Date of Electronic Publication: 2021 May 28.
Publication Year :
2021

Abstract

A series of 43 antiviral corrole-based molecules have been tested on myxoma virus (Lausanne-like T1MYXV strain). An autofluorescent MYXV, with an ANCHOR cassette, has been used for the studies. A <subscript>2</subscript> B-fluorocorroles display various toxicities, from 40 being very toxic (CC <subscript>50</subscript> = 1.7 μM) to nontoxic 38 (CC <subscript>50</subscript> > 50 μM), whereas A <subscript>3</subscript> -fluorocorroles, with one to three fluorine atoms, are not toxic (with the exception of corroles 9 , 10 , and 22 ). In vitro , these compounds show a good selectivity index when used alone. Corrole 35 seems to be the most promising compound, which displays a high selectivity index with the lowest IC <subscript>50</subscript> . Interestingly, this "Hit" corrole is easy to synthesize in a two-step reaction. Upscaling production up to 25 g has been carried out for in vivo tests. In vivo studies on New Zealand white rabbits infected with myxoma virus show that symptoms are delayed and animal weight is increased upon treatment, while no acute toxicity of the corrole molecule was detected.

Details

Language :
English
ISSN :
2373-8227
Volume :
7
Issue :
8
Database :
MEDLINE
Journal :
ACS infectious diseases
Publication Type :
Academic Journal
Accession number :
34048219
Full Text :
https://doi.org/10.1021/acsinfecdis.1c00068