Investigational antiviral therapies for the treatment of influenza

ABSTRACT

Introduction: Influenza viral ribonucleoprotein complexes (vRNPs) play a key role in viral transcription and replication; hence, the recent development of novel anti-influenza drugs targeting vRNPs has garnered widespread interest.

Areas covered: We discuss the function of the constituents of vRNPs and summarize those vRNPs-targeted synthetic drugs that are in preclinical and early clinical development.

Expert opinion: vRNPs contain high-value drug targets; such targets include the subunits PA, PB1, PB2, and NP. Developing a new generation of antiviral therapies with strategies that utilize existing drugs, natural compounds originated from new resources and novel drug combinations may open up new therapeutic approaches to influenza.

KEYWORDS:

• Baloxavir
• influenza virus
• inhibitor
• vRNPs

Article Highlights

• Current limitations of clinically licensed anti-influenza agents have propelled the development of novel approaches that will be vital for combating the threat of pandemic influenza.

• The positive results of baloxavir have encouraged efforts to develop novel inhibitors that target vRNPs.

• The development of lead compounds from natural resources such as marine microorganisms has garnered increasing interest.

• The novel antiviral properties of naproxen may provide valuable insights into the development of new antivirals from existing drugs.

• The combination of anti-influenza drugs with different mechanisms of actions are beneficial for improving therapeutic efficacy and for avoiding drug-resistance.

• Clinical trials will evaluate various antiviral combinations that may be synergistic and less likely to induce breakthrough resistance.

This box summarizes key points contained in the article.

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

This paper is funded in part by government funded grants from the National Natural Science Foundation of China [81772194] awarded to S. Liu and Natural Science Foundation of Guangdong Province [2016A030313591] awarded to J. Yang.