Emerging small and large molecule therapeutics for respiratory syncytial virus

ABSTRACT

Introduction

Respiratory syncytial virus (RSV) causes lower respiratory tract infections and can lead to morbidity and mortality in the infant, elderly and immunocompromised. There is no vaccine and therapeutic interventions are limited. RSV disease research has yielded the development of several prophylactic and therapeutic treatments. Several promising candidates are currently under investigation.

Areas covered

Small and large molecule approaches to RSV treatment were examined and categorized by their mechanism of action using data from PubMed, clinicaltrials.gov, and from the sponsoring organizations publicly available pipeline information. These results are prefaced by an overview of RSV to provide the context for rational therapy development.

Expert opinion

While small molecule drugs show promise for RSV treatment, we believe that large molecule therapy using anti-RSV G and F protein monoclonal antibodies (mAbs) will most efficaciously and safely ameliorate RSV disease.

KEYWORDS:

• Antibodies
• antivirals
• drug
• inhibitor
• monoclonal
• respiratory syncytial virus
• RSV

Article highlights

• RSV adversely affects a diverse section of the population and there are no therapeutics currently available.

• The RSV genome contains several therapeutic targets of interest.

• Small molecule drugs including RSV-specific fusion inhibitors and polymerase inhibitors are being evaluated to target RSV infection cycle to prevent disease.

• Large molecules including monoclonal antibodies target RSV F and G proteins are being examined for prophylactic and post-exposure treatment and have shown promise for RSV disease reduction.

• Human anti-G protein monoclonal antibodies which recognize the RSV G protein central conserved domain neutralize both RSV A and B subtypes in the sub-nanomolar range in the presence of complement.

• Therapeutic intervention is currently limited to monoclonal antibody prophylaxis.

• Technologies including RNAi and drug repurposing are being exploited for the management of RSV disease.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work of the authors is funded by the Georgia Research Alliance.