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 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

Methods of Synthesis and Antiviral Activity of New 4-Alkyl-3-Nitro-1,4-Dihydroazolo[5,1-c][1,2,4]Triazin-4-ols

[Figure not available: see fulltext.] An azo coupling reaction of α-nitro ketones with 5-diazoazoles was used to obtain 4-alkyl-3-nitro-1,4-dihydroazolo[5,1-с][1,2,4]triazines, which were characterized with respect to their antiviral activity against influenza and Coxsackie B3 viruses. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.This study was funded by the Russian Science Foundation (project No. 20-13-00142)

3-Nitro-4-Hydroxy-7-Propargylthio-[1,2,4]Triazolo[5,1c][1,2,4]Triazine And 3-Nitro-4-Hydroxy-7-Ethylthio-[1,2,4]Triazolo[5,1c][1,2,4]Triazine with Antiviral Activity

Изобретение относится к области органической химии, а именно к 3-нитро-4-гидрокси-1,4-дигидро-7-пропаргилтио-[1,2,4]триазоло[5,1с]-[1,2,4]триазину и 3-нитро-4-гидрокси-1,4-дигидро-7-этилтио-[1,2,4]триазоло[5,1с][1,2,4]-триазину, формул 4-5. Технический результат: получены новые гетероциклические соединения, обладающие противовирусной активностью в отношении энтеровирусов. 1 табл., 5 пр.FIELD: organic chemistry. SUBSTANCE: invention relates to the field of organic chemistry, namely to 3-nitro-4-hydroxy-1,4-dihydro-7-propargylthio-[1,2,4]triazolo[5,1c]-[1,2,4]triazine and 3-nitro-4-hydroxy-1,4-dihydro-7-ethylthio-[1,2,4]triazolo[5,1c][1,2,4]triazine of formulas 4-5. EFFECT: new heterocyclic compounds are obtained, having an antiviral activity relatively to enteroviruses. 1 cl, 1 tbl, 5 ex