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

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 2 B-fluorocorroles display various toxicities, from 40 being very toxic (CC 50 = 1.7 μM) to nontoxic 38 (CC 50 > 50 μM), whereas A 3 -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 50 . 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.

Evaluation of Commercial Myxomatosis Vaccines against Recombinant Myxoma Virus (ha-MYXV) in Iberian Hare and Wild Rabbit

“…This can mean that 100 ffu might be a low dose for a viral challenge by subcutaneous route, and is why a dose of 1000 ffu was used in the challenge carried out on rabbits, bearing in mind that this test was made after that of hares. Studies carried out in rabbits used different viral doses, namely 2 × 10 5.4 TCID50 (around 1.4 × 10 5.4 ffu) [ 31 ], unknown viral load [ 32 ] inoculated subcutaneously, or a dose of around 10 2 to 10 4 [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ] inoculated intradermically.…”

Milestones and Most Recent Advances in Corrole’s Science and Technology

“…The latest example was performed on the zebra fish model of the still cureless amyotrophic lateral sclerosis (ALS) disease . Some new corroles were also introduced as potential agents against human Cytomegalovirus infection. − …”

Virus tracking technologies and their applications in viral life cycle: research advances and future perspectives

“…If ParB proteins fuse with FPs, their accumulation on the ANCH target sequence and spread to adjacent sequences will form fluorescence focuses being easy to detect, enabling the identification of ANCHOR-labeled DNA sites (57,58). The ANCHOR system has been successfully used to analyze the infection and replication process of various virus, such as human cytomegalovirus (HCMV) (59), vaccinia virus (60), and baculovirus, and the myxoma virus based on the ANCHOR system can be used to evaluate antiviral drugs (61,62). The ANCHOR system has been proven not to disrupt the structure and function of chromatin, despite the presence of up to 500 ParB proteins on and around the ANCH sequence (63).…”