Influenza antivirals and their role in pandemic preparedness

Abstract

Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two classes of viral protein-targeting drugs, neuraminidase inhibitors and polymerase inhibitors, are approved for influenza treatment and post-exposure prophylaxis. Resistance to both classes has been documented, highlighting the need to develop novel antiviral options that may include both viral and host-targeted inhibitors. Such efforts will form the basis of management of seasonal influenza infections and of strategic planning for future influenza pandemics. This review focuses on the two classes of approved antivirals, their drawbacks, and ongoing work to characterize novel agents or combination therapy approaches to address these shortcomings. The importance of these topics in the ongoing process of influenza pandemic planning is also discussed.

Keywords: Antiviral drug; Baloxavir; Influenza virus; Neuraminidase inhibitor; Pandemic.

Influenza antiviral drugs in clinical-stage active development that have received post-marketing approval in the United States. Additional drugs marked as having received conditional approval (Inavir—Japan only) or limited approval (Arbidol—Russia and China only; Inavir—Japan only). The compounds are indicated by name with the company sponsoring their development; color-coded boxes indicate the route of administration. CENI—cap-dependent endonuclease inhibitor targeting the PA protein; NAI—neuraminidase inhibitor targeting the NA protein; mAb—monoclonal antibody targeting the HA protein; MEK inhibitor—mitogen-activated protein kinase; TLR—toll-like receptor; NSAID—non-steroidal anti-inflammatory drug; MOA—monoamine oxidase inhibitor.