Development of antiviral therapeutics combating coxsackievirus type B3 infection

Enteroviruses comprise highly diverse group of single-stranded positive RNA viruses belonging to Enterovirus genus, Picornaviridae family. They are the most prevalent viruses worldwide highlighted by high resistance to environmental cues. Enteroviruses normally cause seasonal self-limiting infection...

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Autores principales:	A. S. Volobueva, V. V. Zarubaev, K. S. Lantseva
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2021
Materias:	enteroviruses coxsackievirus infection myocarditis antivirals drug development inhibitor Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/f6757e8509a44ad6863f8ab67261cef2
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spelling	oai:doaj.org-article:f6757e8509a44ad6863f8ab67261cef22021-11-22T07:09:55ZDevelopment of antiviral therapeutics combating coxsackievirus type B3 infection2220-76192313-739810.15789/2220-7619-DOA-1273https://doaj.org/article/f6757e8509a44ad6863f8ab67261cef22021-02-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/1273https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Enteroviruses comprise highly diverse group of single-stranded positive RNA viruses belonging to Enterovirus genus, Picornaviridae family. They are the most prevalent viruses worldwide highlighted by high resistance to environmental cues. Enteroviruses normally cause seasonal self-limiting infections, but also known as causative infectious agents of encephalitis, myocarditis, poliomyelitis, acute heart failure and sepsis. Enterovirus genetic plasticity contributes to widespread epidemics and sporadic outbreaks (e. g., outbreaks of Enterovirus D68 and Enterovirus 71). Type B Coxsackieviruses of Enterovirus B species is one of commonly identified infectious agents associated predominantly with mild upper respiratory and gastrointestinal illnesses. Nevertheless, Coxsackieviruses B3 infection can result in severe myocarditis leading ultimately to heart failure. The pathogenesis of Coxsackievirus B3-induced myocarditis is well known being mediated by both direct damage due to viral proteases and indirectly via secondary host immune responses. Despite success in preventive vaccination of some enterovirus infections that allowed to control some of them direct antiviral agents for treatment of enteroviral infection particularly Coxsackieviruses B3 myocardial infection are still in demand. In addition, no ongoing clinical trials for therapy or prevention of Coxsackieviruses B3 infection are available. Current treatment strategies are mainly aimed to stabilize patient condition and relieve discomfort condition. It seems that relatively small market for anti-enteroviral drugs prevents pharma industry from developing new drugs. The Coxsackieviruses B3 lifecycle have been extensively studied and potential targets for drug design have been identified. The aim of our review was to describe current state in the field of antiviral drug design combating Coxsackieviruses B3 infection emphasizing direct-acting antivirals, albeit paying some attention to host factor-targeting inhibitors (including compounds from medicinal plant extracts) as well. The following categories of direct Coxsackieviruses B3 inhibitors are discussed in detail: capsid binders (pleconaril and its derivatives), viral 3C protease inhibitors (rupintrivir and its analogs), drugs targeting viral replication (both nucleoside analogs and non-nucleoside inhibitors). Results of drug repurposing screens for amiloride, benzerazide, dibucaine and fluoxetine are also discussed.A. S. VolobuevaV. V. ZarubaevK. S. LantsevaSankt-Peterburg : NIIÈM imeni Pasteraarticleenterovirusescoxsackievirusinfectionmyocarditisantiviralsdrug developmentinhibitorInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 11, Iss 1, Pp 57-67 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	enteroviruses coxsackievirus infection myocarditis antivirals drug development inhibitor Infectious and parasitic diseases RC109-216
spellingShingle	enteroviruses coxsackievirus infection myocarditis antivirals drug development inhibitor Infectious and parasitic diseases RC109-216 A. S. Volobueva V. V. Zarubaev K. S. Lantseva Development of antiviral therapeutics combating coxsackievirus type B3 infection
description	Enteroviruses comprise highly diverse group of single-stranded positive RNA viruses belonging to Enterovirus genus, Picornaviridae family. They are the most prevalent viruses worldwide highlighted by high resistance to environmental cues. Enteroviruses normally cause seasonal self-limiting infections, but also known as causative infectious agents of encephalitis, myocarditis, poliomyelitis, acute heart failure and sepsis. Enterovirus genetic plasticity contributes to widespread epidemics and sporadic outbreaks (e. g., outbreaks of Enterovirus D68 and Enterovirus 71). Type B Coxsackieviruses of Enterovirus B species is one of commonly identified infectious agents associated predominantly with mild upper respiratory and gastrointestinal illnesses. Nevertheless, Coxsackieviruses B3 infection can result in severe myocarditis leading ultimately to heart failure. The pathogenesis of Coxsackievirus B3-induced myocarditis is well known being mediated by both direct damage due to viral proteases and indirectly via secondary host immune responses. Despite success in preventive vaccination of some enterovirus infections that allowed to control some of them direct antiviral agents for treatment of enteroviral infection particularly Coxsackieviruses B3 myocardial infection are still in demand. In addition, no ongoing clinical trials for therapy or prevention of Coxsackieviruses B3 infection are available. Current treatment strategies are mainly aimed to stabilize patient condition and relieve discomfort condition. It seems that relatively small market for anti-enteroviral drugs prevents pharma industry from developing new drugs. The Coxsackieviruses B3 lifecycle have been extensively studied and potential targets for drug design have been identified. The aim of our review was to describe current state in the field of antiviral drug design combating Coxsackieviruses B3 infection emphasizing direct-acting antivirals, albeit paying some attention to host factor-targeting inhibitors (including compounds from medicinal plant extracts) as well. The following categories of direct Coxsackieviruses B3 inhibitors are discussed in detail: capsid binders (pleconaril and its derivatives), viral 3C protease inhibitors (rupintrivir and its analogs), drugs targeting viral replication (both nucleoside analogs and non-nucleoside inhibitors). Results of drug repurposing screens for amiloride, benzerazide, dibucaine and fluoxetine are also discussed.
format	article
author	A. S. Volobueva V. V. Zarubaev K. S. Lantseva
author_facet	A. S. Volobueva V. V. Zarubaev K. S. Lantseva
author_sort	A. S. Volobueva
title	Development of antiviral therapeutics combating coxsackievirus type B3 infection
title_short	Development of antiviral therapeutics combating coxsackievirus type B3 infection
title_full	Development of antiviral therapeutics combating coxsackievirus type B3 infection
title_fullStr	Development of antiviral therapeutics combating coxsackievirus type B3 infection
title_full_unstemmed	Development of antiviral therapeutics combating coxsackievirus type B3 infection
title_sort	development of antiviral therapeutics combating coxsackievirus type b3 infection
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2021
url	https://doaj.org/article/f6757e8509a44ad6863f8ab67261cef2
work_keys_str_mv	AT asvolobueva developmentofantiviraltherapeuticscombatingcoxsackievirustypeb3infection AT vvzarubaev developmentofantiviraltherapeuticscombatingcoxsackievirustypeb3infection AT kslantseva developmentofantiviraltherapeuticscombatingcoxsackievirustypeb3infection
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Development of antiviral therapeutics combating coxsackievirus type B3 infection

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