Preparing for the next viral threat with broad-spectrum antivirals

Abstract

There is a large global unmet need for the development of countermeasures to combat hundreds of viruses known to cause human disease and for the establishment of a therapeutic portfolio for future pandemic preparedness. Most approved antiviral therapeutics target proteins encoded by a single virus, providing a narrow spectrum of coverage. This, combined with the slow pace and high cost of drug development, limits the scalability of this direct-acting antiviral (DAA) approach. Here, we summarize progress and challenges in the development of broad-spectrum antivirals that target either viral elements (proteins, genome structures, and lipid envelopes) or cellular proviral factors co-opted by multiple viruses via newly discovered compounds or repurposing of approved drugs. These strategies offer new means for developing therapeutics against both existing and emerging viral threats that complement DAAs.

Figure 1. Toward broad-spectrum antivirals.

Antiviral drugs that selectively inhibit unique viral proteins typically provide a narrow-spectrum solution (left), whereas broad-spectrum drugs can restrict multiple viruses by inhibiting either common viral functions or structures (middle) or host factors commonly required by several viruses (right). Adapted with permission from Science (204).

Figure 2. Approved and experimental direct-acting compounds with broad-spectrum antiviral activity.

Depicted here is a generic viral life cycle. Examples of classes of inhibitors with broad-spectrum antiviral activity are connected to the specific stages of the viral life cycle or cellular process they target.

Figure 3. Approved and experimental host-targeted compounds with broad-spectrum antiviral activity.

Depicted here is a generic viral life cycle. Examples of classes of inhibitors with broad-spectrum antiviral activity are connected to the specific stage(s) of the viral life cycle or cellular process they target.