Enterovirus Diseases and Vaccines

Enterovirus A71 (EV A71) (genus enterovirus, family pircornaviridae) causes benign vesicular lesions on skin (hand, foot and mouth disease, HFMD) and mucous membranes of the mouth (herpangina), and also severe to life-threatening infections of the brain, the heart, and other internal organs. Disease outbreaks in the Asia-Pacific region regularly involve thousands of children <5 years resulting in many deaths. Such outbreaks are caused by specific EV genotypes that vary by time and place. While there are various promising and innovative options for treatment in development, none are licensed to date. Immunoglobulins may be beneficial through virus neutralization and modulation of the inflammatory response by the host. In China, 3 different highly efficacious and safe vaccines are commercially available; however, none are licensed outside the country. Roughly half a dozen vaccines are in the development pipeline, with some using innovative approaches and trying to broaden strain coverage.

Development of Group B Coxsackievirus as an Oncolytic Virus: Opportunities and Challenges

Oncolytic viruses have emerged as a promising strategy for cancer therapy due to their dual ability to selectively infect and lyse tumor cells and to induce systemic anti-tumor immunity. Among various candidate viruses, coxsackievirus group B (CVBs) have attracted increasing attention in recent years. CVBs are a group of small, non-enveloped, single-stranded, positive-sense RNA viruses, belonging to species human Enterovirus B in the genus Enterovirus of the family Picornaviridae. Preclinical studies have demonstrated potent anti-tumor activities for CVBs, particularly type 3, against multiple cancer types, including lung, breast, and colorectal cancer. Various approaches have been proposed or applied to enhance the safety and specificity of CVBs towards tumor cells and to further increase their anti-tumor efficacy. This review summarizes current knowledge and strategies for developing CVBs as oncolytic viruses for cancer virotherapy. The challenges arising from these studies and future prospects are also discussed in this review.

Antivirals blocking entry of enteroviruses and therapeutic potential

Viruses from the genus Enterovirus (EV) of the Picornaviridae family are known to cause diseases such as hand foot and mouth disease (HFMD), respiratory diseases, encephalitis and myocarditis. The capsid of EV is an attractive target for the development of direct-acting small molecules that can interfere with viral entry. Some of the capsid binders have been evaluated in clinical trials but the majority have failed due to insufficient efficacy or unacceptable off-target effects. Furthermore, most of the capsid binders exhibited a low barrier to resistance. Alternatively, host-targeting inhibitors such as peptides derived from the capsid of EV that can recognize cellular receptors have been identified. However, the majority of these peptides displayed low anti-EV potency (µM range) as compared to the potency of small molecule compounds (nM range). Nonetheless, the development of anti-EV peptides is warranted as they may complement the small-molecules in a drug combination strategy to treat EVs. Lastly, structure-based approach to design antiviral peptides should be utilized to unearth potent anti-EV peptides.

Multifunctionality of structural proteins in the enterovirus life cycle

Members of the genus Enterovirus have a significant effect on human health, especially in infants and children. Since the viral genome has limited coding capacity, Enteroviruses subvert a range of cellular processes for viral infection via the interaction of viral proteins and numerous cellular factors. Intriguingly, the capsid–receptor interaction plays a crucial role in viral entry and has significant implications in viral pathogenesis. Moreover, interactions between structural proteins and host factors occur directly or indirectly in multiple steps of viral replication. In this review, we focus on the current understanding of the multifunctionality of structural proteins in the viral life cycle, which may constitute valuable targets for antiviral and therapeutic interventions.

A44 Genome analysis of bovine enterovirus variants isolated from cattle in Thailand

Bovine enteroviruses (BEV) are non-enveloped RNA viruses of the genus Enterovirus, family Picornaviridae, which are commonly found in cattle. They have been classified into two species, enterovirus E (EV-E) and enterovirus F (EV-F). The viruses were previously considered non-pathogenic, but recent evidences suggest their association with pathogenesis in cattle. BEV-like enteroviruses have also been increasingly isolated from a wide range of animals, such as sheep, goats, horses, geese, possum, and deer, from many countries. The isolation and characterization of novel enteroviruses expands the range of the genus. Our data show that both EV-E and EV-F are circulating in cattle in Thailand. The viruses have been detected in 35–67 per cent of dairy and meat cattle feces in Kanchanaburi Province. Recently, we retrieved EV-E isolates from cattle feces by virus isolation in Madin-Darby Bovine Kidney cells. Four virus isolates were subjected to whole-genome sequencing using Illumina next-generation sequencing. A phylogenetic analysis of VP1 capsid protein, which is used for virus genotyping, suggested that there are at least two EV-E genotypes circulating in cattle in the area of study. Two virus strains, closely related to EV-E1 with amino acid sequence identities >88 per cent were identified as EV-E1. The other two strains, closely related to EV-E2 with amino acid sequence identities < 85 per cent, were likely to constitute a new EV-E genotype separate from the existing EV-E2.

Development of Echovirus 29 cytopathology in RD cell line might not happen within 10 days post inoculation

ABSTRACTEchovirus 29 (E29) is a member of Species Enterovirus B (EV-B) in the genus Enterovirus, family Picornaviridae, order Picornavirinae. In Nigeria, molecular characterization of E29 was first described in 2002. In 2015, we found that a new clade of E29 had replaced that described in Nigeria in 2002-2003. To date, E29 isolates described from Nigeria were isolated in cultures of RD cell line. In 2016, we characterised an E29 strain that did not show cytopathology on RD cell line within the recommended 10 days of culture.Here we show that the E29 in question grows with evident CPE in RD cell culture like other members of the clade when allowed to stay in culture for 13 to 14 days. The findings of this study therefore suggest that some of the samples declared negative for enteroviruses by the current WHO cell culture based detection algorithm might be false negatives. It is therefore encouraged that those particularly interested in non-polio enteroviruses endeavour to maintain at least 14 days incubation in cell culture in a bid to accommodate NPEVs like E29 that might need longer time to develop CPE especially when present at low titre.