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Neuroinfectious Diseases
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Jeremy D. Young, Jesica A. Herrick, Scott Borgetti
Treatment – Pleconaril has in vitro activity against enteroviruses and may be beneficial for serious infections.10 However, there are not enough clinical data to recommend its use. Therefore, management of enteroviral meningitis is supportive, with no indication at this time for antiviral agents.
Enteroviruses
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Karen Straube-West, Burk Jubelt
Although current treatment of viral meningitis is mostly supportive, specific agents are under study. Pleconaril is an antiviral agent specific for enteroviruses. Pleconaril has been shown to be effective at interfering with viral replication. Studies indicate that pleconaril is effective in treating enteroviral meningitis (38%–50% improvement in drug group vs. placebo) [33].
Viral infections
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Supportive care suffices in most of the enteroviral infections as it is self-limiting. However, in certain patient populations, including immunosuppressed individuals or neonates, an enteroviral infection may be associated with potentially life-threatening complications. Pleconaril, a drug that interferes with enterovirus attachment and uncoating by binding to the protein capsid, has been demonstrated to be useful in clinical studies, and it holds promise as a specific antiviral therapy for serious enteroviral infections [22].
Enteroviruses and coronaviruses: similarities and therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2021
Varpu Marjomäki, Kerttu Kalander, Maarit Hellman, Perttu Permi
-Enteroviruses have been shown to possess more than one binding pocket that are associated with stability and receptor binding of the virions. The canonical hydrophobic pocket of enteroviruses has long been considered to be involved with the stability of the viruses [66]. The aliphatic fatty acids inside the pockets are typically partially or totally lost during the opening of the virion structure and RNA release. Therefore, various drugs have been developed to replace the fatty acid with a stronger binder to confer stability and possibly to interfere with receptor binding and cell entry. After development of Pleconaril, several other molecules have also been developed with great efficacy as inhibitors of infection [67]. In addition to the hydrophobic pocket found underneath the structural protein 1 in every protomer, 60 sites in total for 1 enterovirus, another druggable pocket was also recently discovered involving another area on the virus surface and found in both rhinoviruses and other and enteroviruses [68]. There will probably be more discoveries of new druggable areas in the enteroviruses as well as coronaviruses. It will thus be important to screen molecular libraries and search for drugs that show the potential of inhibiting several viruses. In addition to finding such molecules, it will be important to understand the mechanism of action behind the inhibitory effect. This will then help to develop even more effective future drugs with suitable pharmacokinetics and real use as future drugs.
Human rhinovirus infection and COPD: role in exacerbations and potential for therapeutic targets
Published in Expert Review of Respiratory Medicine, 2020
John Cafferkey, James Andrew Coultas, Patrick Mallia
Most anti-rhinovirus therapies developed to date have focussed on anti-capsid properties, though protease inhibitors have also been trialed. Pleconaril was the first antiviral therapy to undergo clinical trials in humans. It is an orally administered viral capsid-function inhibitor that inhibits viral replication of around 90% of HRV serotypes. Pleconaril integrates into the hydrophobic regions of the capsid protein VP1 and prevents HRV attachment and uncoating [140]. Two double-blind, randomized, placebo-controlled trials showed pleconaril reduced both the duration (by 1 day) and severity of HRV common colds and accelerated viral clearance [141]. A Phase II trial exploring the effects of intranasally administered pleconaril in HRV-induced asthma exacerbations showed no effect compared to placebo (ClinicalTrials.gov 2015). Pleconaril was not licensed by the FDA as the potential adverse effects of hepatic enzyme induction were felt to outweigh a modest reduction in symptoms of the common cold. Vapendavir is another capsid-function inhibitor and binds to a similar region of the capsid proteins though with a possible stronger binding interaction [142]. A 2017 phase IIb trial exploring its anti-HRV effects in asthmatics did not show any benefit [143]. Pirodavir is another capsid function inhibitors binding at VP1 [144]. A phase III clinical trial in healthy individuals with naturally-acquired HRV common colds showed a reduction in viral shedding but no reduction in either the severity or duration of clinical illness [145].