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Recent developments in antiviral agents against enterovirus 71 infection.

Tan CW, Lai JK, Sam IC, Chan YF - J. Biomed. Sci. (2014)

Bottom Line: Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals.The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine.The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. chanyf@ummc.edu.my.

ABSTRACT
Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

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Related in: MedlinePlus

Schematic illustration of EV-71 intracellular infection and summary of the antiviral agents. The antiviral agents are classified according to their mechanism of actions, which include molecular decoys, receptor antagonists, uncoating inhibitors, translation inhibitors, polyprotein processing inhibitors and replication inhibitors.
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Figure 1: Schematic illustration of EV-71 intracellular infection and summary of the antiviral agents. The antiviral agents are classified according to their mechanism of actions, which include molecular decoys, receptor antagonists, uncoating inhibitors, translation inhibitors, polyprotein processing inhibitors and replication inhibitors.

Mentions: Figure 1 and Table 1 summarizes all the potential targets of antivirals and lists the recent antiviral agents with significant antiviral activities against EV-71 infection as discussed above. Amongst these drugs, modified WIN compounds are antivirals with the lowest IC50. Only bovine lactoferrin, pleconaril, shRNA, siRNA, rupintrivir, ribavirin and 17-AAG have been tested in vivo. Ribavirin and amantadine are already in clinical use for other viruses, and rupintrivir and pleconaril are in clinical development.


Recent developments in antiviral agents against enterovirus 71 infection.

Tan CW, Lai JK, Sam IC, Chan YF - J. Biomed. Sci. (2014)

Schematic illustration of EV-71 intracellular infection and summary of the antiviral agents. The antiviral agents are classified according to their mechanism of actions, which include molecular decoys, receptor antagonists, uncoating inhibitors, translation inhibitors, polyprotein processing inhibitors and replication inhibitors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3924904&req=5

Figure 1: Schematic illustration of EV-71 intracellular infection and summary of the antiviral agents. The antiviral agents are classified according to their mechanism of actions, which include molecular decoys, receptor antagonists, uncoating inhibitors, translation inhibitors, polyprotein processing inhibitors and replication inhibitors.
Mentions: Figure 1 and Table 1 summarizes all the potential targets of antivirals and lists the recent antiviral agents with significant antiviral activities against EV-71 infection as discussed above. Amongst these drugs, modified WIN compounds are antivirals with the lowest IC50. Only bovine lactoferrin, pleconaril, shRNA, siRNA, rupintrivir, ribavirin and 17-AAG have been tested in vivo. Ribavirin and amantadine are already in clinical use for other viruses, and rupintrivir and pleconaril are in clinical development.

Bottom Line: Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals.The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine.The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. chanyf@ummc.edu.my.

ABSTRACT
Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

Show MeSH
Related in: MedlinePlus