Challenges with the discovery of RNA-based therapeutics for flaviviruses

ABSTRACT

Introduction

Flaviviruses are emerging or reemerging pathogens that have caused several outbreaks throughout the world and pose serious threats on human health and economic development. RNA-based therapeutics are developing rapidly, and hold promise in the fight against flaviviruses. However, to develop efficient and safe therapeutics for flaviviruses, many challenges remain unsolved.

Areas covered

In this review, the authors briefly introduced the biology of flaviviruses and the current advances in RNA-based therapeutics for them. Furthermore, the authors list the challenges and possible solutions in this area. Finally, the authors give their opinion on the development and future of RNA-based therapeutics for flaviviruses.

Expert opinion

With the rapid development of structural biology, the crystal structures of flavivirus proteins may lay the foundation for future rational drug design. Studies regarding the interactions between the flavivirus and the host will also be invaluable to inhibitor design. Researchers should maintain the current momentum to bring about safe and effective anti-flavivirus drugs to licensure through joint efforts of academia, government, and industry.

KEYWORDS:

• Flaviviruses
• RNA-based therapeutics
• ASOs
• RNA aptamers
• RNA interference

Article highlights

• In light of the ongoing pandemics, there is an urgent need to accelerate the development and refinement of RNA-based therapeutics for flaviviruses.

• Currently, achievements have been made in different types of RNA-based therapeutics for flaviviruses, including ASOs, RNA aptamers, miRNAs/siRNA, shRNAs, and ribozymes.

• The challenges associated with specificity, delivery, tolerability, and viral escape have greatly hampered the use of RNA-based therapeutics from entering clinical trials.

• Possible solutions such as progress in high-throughput screening technologies, advances in different kinds of nanoparticles, improvement in the construction of non-human primate models, multiple RNAi, combination with other antiviral approaches, and lyophilization may facilitate the battle against flaviviruses.

• The structures that are critical for the replication of flaviviruses are also promising antiviral targets.

Declaration of interest

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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

The authors are supported by the National Natural Science Foundation of China, the Key Medical Science and Technology Program of Shanxi Province, the Applied Basic Research Program of Shanxi Province, and the Shanxi “1331” Project and Efficiency Improvement Plan.