Intranasal antivirals against respiratory syncytial virus: the current therapeutic development landscape

ABSTRACT

Introduction

Respiratory syncytial virus (RSV) causes bronchiolitis and other respiratory issues in immunocompromised individuals, the elderly, and children. After six decades of research, we have only recently seen the approval of two RSV vaccines, Arexvy and Abrysvo. Direct-acting antivirals against RSV have been more difficult to develop with ribavirin and palivizumab giving very modest reductions in hospitalizations and no differences in mortality. Recently, nirsevimab was licensed and has proven to be much more effective when given prophylactically. These are delivered intravenously (IV) and intramuscularly (IM), but an intranasal (IN) antiviral has several advantages in terms of ease of use, lower resource need, and acting at the site of infection.

Areas covered

In this paper, we review the available literature on the current pre-clinical research landscape of anti-RSV therapeutics tested for IN delivery.

Expert opinion

As RSV is a respiratory virus that infects both the upper and lower respiratory tracts, efforts are focused on developing a therapeutic that can be delivered via the nasal route. The rationale is to directly target the replicating virus with an obvious respiratory tract tropism. This approach will not only pave the way for a nasal delivery approach aimed at reducing respiratory viral illness but also controlling aerosol virus transmission.

KEYWORDS:

• Antiviral
• intranasal
• respiratory syncytial virus
• siRNA
• therapeutics

Article highlights

• Intranasal antivirals targeting RSV represent a promising approach to combat this significant public health concern, particularly among infants, young children, and the elderly.

• Current therapeutic development strategies for RSV intranasal antivirals include RSVtargeting, host-targets, and nucleic acid (NA)-based antivirals (Figure 1), each offering unique advantages in terms of efficacy and ease of administration.

• Challenges in RSV antiviral development include producing an effective intranasal RSV therapy, the adaptability of the virus, ensuring safety and affordability, and addressing the seasonal nature of RSV outbreaks.

• Collaborative efforts between academia, industry, and regulatory agencies are vital to expedite the evaluation and approval of effective IN antiviral therapeutics, improving our ability to prevent RSV infections.

Declaration of interest

N.A.J.M is a consultant for Prorenata Biotech. The authors have no other 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

This paper was not funded.