Enterovirus D68 Antivirals: Past, Present, and Future

Hu, Yanmei; Musharrafieh, Rami; Zheng, Madeleine; Wang, Junyang

doi:10.1021/acsinfecdis.0c00120

Cited by 44 publications

(40 citation statements)

References 102 publications

(251 reference statements)

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“…In addition, immune suppressive therapies have also been used by some centers to target the inflammatory response to infection [ 131 ]. It should be noted that recently much progress has been made in the development of the EV-D68 antivirals by targeting various viral proteins and host factors essential for viral replication [ 132 ]. However, this intervention was not associated with improved neurologic outcomes [ 133 ].…”

Section: Discussionmentioning

confidence: 99%

Global prevalence and case fatality rate of Enterovirus D68 infections, a systematic review and meta-analysis

et al. 2022

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A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1–5.0) and 66.3% (95% CI = 40.0–88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.

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Section: Discussionmentioning

confidence: 99%

Global prevalence and case fatality rate of Enterovirus D68 infections, a systematic review and meta-analysis

et al. 2022

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“…As a result, most antiviral research has targeted this virus. Several antiviral strategies have been proposed (reviewed in References [ 165 , 166 ]) such as capsid-binding compounds [ 145 , 167 , 168 , 169 , 170 , 171 ], viral proteases’ inhibitors [ 168 , 169 , 172 , 173 , 174 ], drugs targeting the non-structural proteins 2C [ 168 , 175 , 176 ], 3A [ 167 , 168 , 169 , 177 ], the viral polymerase 3D [ 167 , 169 , 178 , 179 ] and drugs blocking translation [ 180 ]. However, even the most favourable candidates did not obtain promising results in the mouse models [ 175 , 181 ].…”

Section: Discussionmentioning

confidence: 99%

Enterovirus D: A Small but Versatile Species

et al. 2021

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Enteroviruses (EVs) from the D species are the causative agents of a diverse range of infectious diseases in spite of comprising only five known members. This small clade has a diverse host range and tissue tropism. It contains types infecting non-human primates and/or humans, and for the latter, they preferentially infect the eye, respiratory tract, gastrointestinal tract, and nervous system. Although several Enterovirus D members, in particular EV-D68, have been associated with neurological complications, including acute myelitis, there is currently no effective treatment or vaccine against any of them. This review highlights the peculiarities of this viral species, focusing on genome organization, functional elements, receptor usage, and pathogenesis.

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“…The viral proteins that are being exploited as targets to develop anti-EV-D68 agents are those for which inhibitors were selected in the anti-HRV drug discovery process, since their high degree of sequence conservation among different enteroviruses might allow for broad-spectrum antiviral activity. 104 As an example, fluoxetine-modified inhibitors with broad spectrum activity against enteroviruses and rhinoviruses have been reported that target the non-structural 2C protein. 105 This protein has been proposed to play multifunctional roles in the viral life cycle of nonpolio enteroviruses, and significant efforts are being made in identifying antivirals against this target.…”

Section: Rhinovirusesmentioning

confidence: 99%