Study of the Biological Activity of Novel Synthetic Compounds with Antiviral Properties against Human Rhinoviruses

Abstract

Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir’s main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI) on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602) resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir’s central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses.

In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

“…Vapendavir (Biota Holdings), a benzisoxazole analogue of pirodavir, is currently in clinical development for the treatment of rhinovirus-induced asthma exacerbations [ 9 ]. In the past, we explored the antiviral activity of a panel of pirodavir analogues with modifications of the central hydrocarbon chain [ 10 , 11 ]. Here, we report on the particular characteristics of the antiviral activity and mode of action of a novel and the until now most potent and least toxic analogue in this series (Fig.…”

Broad reactivity of the Luminex xTAG Respiratory Virus Panel (RVP) assay for the detection of human rhinoviruses

“…1 With the advent of new antivirals directed at the treatment of serious HRV infections it is becoming increasingly important to detect a broad range of HRV strains so that targeted antiviral therapy can be appropriated instituted. 2,3 The xTAG Respiratory Virus Panel (RVP, Luminex Molecular Diagnostics, Toronto, Canada) is a US Food and Drug Administration (US FDA) cleared multiplex nucleic acid amplification test for the detection of respiratory viruses including adenovirus (ADV), human metapneumovirus (hMPV), influenza A (influA with subtyping of seasonal H1 and seasonal H3), influenza B (influB), parainfluenza types 1 (PIV-1), 2 (PIV-2) and 3 (PIV-3), respiratory syncytial virus (RSV) A and B, and HRV. Some enteroviral (EV) strains are also detected due to cross reactivity with HRV and therefore the assay does not distinguish between HRV and EV.…”

Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds

“…The purpose of the present study was to explore the antiviral potential of the above-mentioned compounds together with an additional set of similar substances (compounds [6002-6702]) 15 on the replication of a selection of other human pathogen enteroviruses, namely EV71, poliovirus 1 (PV1), coxsackievirus B3 (CVB3), and echovirus11 (ECHO11). The synthesis and chemical properties of the molecules of the series [6c-10c] were previously described by Bernard et al, 14 and also by Laconi et al 15 for those of series [6002-6702].…”

“…The synthesis and chemical properties of the molecules of the series [6c-10c] were previously described by Bernard et al., 14 and also by Laconi et al. 15 for those of series [6002–6702] . Pleconaril was kindly provided by V. Makarov (RAS, Institute of Biochemistry, Russia).…”