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New therapies for acute RSV infections: where are we?

  • Ying Xing
  • Marijke Proesmans
Review

Abstract

Respiratory syncytial virus (RSV) infection is one of the main causes of infant hospitalization and mortality. The single-stranded RNA virus codes for 11 proteins of which the F protein, a surface epitope responsible for RSV fusion, is the most targeted for developing antiviral medicines and vaccines. The peak of symptoms occurs around day 4 to 6 of illness and the airway obstruction is merely caused by the host immune inflammatory response. Risk factors for severe bronchiolitis are prematurity, comorbidity, and/or being immunocompromised. At present, there are no curative therapies available for RSV infections and treatment is supportive only. Development of new antiviral medicines is however promising. The aim of this review is to give a summary of the most important new antiviral therapies in clinical development for RSV infection and to explain their mode of action. We therefore performed a literature search on this topic.

Conclusion: There are currently at least eight antivirals being investigated in clinical trials. They all use different approaches to either focus on preventing viral fusion with host cells or inhibiting virus replication. Some target RSV surface epitopes like the F protein to halt fusion, others aim for RNA chain termination, while small interfering RNAs downregulate viral protein production.

What is known:

• RSV bronchiolitis is a very important pediatric disease as it is one of the main causes of infant hospitalization and mortality. By the age of 2 years, 95% of all the infants worldwide will have been infected.

• The only recommended therapy is supportive since there are no existing curative therapies yet.

What this study adds:

• This review gives an overview of the current progress in the research field of RSV antivirals with background information on their mode of action.

Keywords

RSV Bronchiolitis Antiviral medication-mode of action 

Abbreviations

AAP

American Academy of Pediatrics

AE

Adverse effects

BOS

Bronchiolitis obliterans syndrome

CMP

Cytidine monophosphate

Ig

Immunoglobulin

IVIG

Intravenous immunoglobulin

LRTI

Lower respiratory tract infection

miRNA

MicroRNA

NICE

National Institute for Health Care and Excellence

RISC

RNA-induced silencing complex

RNAi

RNA interference

RSV

Respiratory syncytial virus

siRNA

Small interfering RNA

SNP

Single-nucleotide polymorphism

TEAE

Treatment-emergent adverse effects

Notes

Authors’ contributions

Ying Xing performed the literature search and selection of articles with supervision of Marijke Proesmans. The first article draft was written by Ying Xing. Marijke Proesmans extensively worked with her towards the final draft.

Compliance with ethical statements

Conflict of interest

Ying Xing has no conflict of interest to declare. Marijke Proesmans is the principal investigator for the drugs JNJ-53718678 and ALX-0171.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study: not applicable for this type of manuscript.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Development and Regeneration, Cluster Organ Systems, Biomedical SciencesKU LeuvenLeuvenBelgium
  2. 2.Department of Paediatric Pulmonology, University Hospital LeuvenUniversity of LeuvenLeuvenBelgium

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