BROAD-SPECTRUM ANTIVIRALS: CURRENT ADVANCES, MECHANISMS, AND PANDEMIC PREPAREDNESS
Emerging infectious diseases present an escalating global health threat, with pandemic-scale outbreaks occurring at an estimated frequency of every 33-50 years. Traditional antiviral development focused on virus-specific compounds has proven inadequate for responding to novel pathogens, as demonstrated by the rapid emergence of drug-resistant SARS-CoV-2 variants and the persistent vulnerability of populations lacking therapeutics for hundreds of known human viruses.
This comprehensive review examines broad-spectrum antivirals as a paradigm shift in pandemic preparedness and therapeutic strategy. We synthesize current knowledge across two primary mechanistic classes: Direct-Acting Antivirals (DAAs) targeting conserved viral replication machinery through viral entry inhibitors, polymerase inhibitors, and protease inhibitors; and Host-Targeting Antivirals (HTAs) exploiting conserved cellular dependencies including kinase inhibitors, metabolic pathway modulators, and immune system enhancers.
The review further explores natural product-derived antivirals from plants, marine organisms, and fungi as underexploited sources of broad-spectrum compounds with multi-target mechanisms. Integration of artificial intelligence, machine learning, and computational chemistry has substantially accelerated compound discovery and target identification. Clinical pipelines now include diverse mechanistic classes with Emergency Use Authorization pathways enabling rapid deployment. However, critical challenges persist, including achieving both potency and selectivity, managing antiviral resistance through combination therapy and surveillance, navigating regulatory frameworks for prophylactic use, and overcoming economic barriers to development.
Recommendations include government-funded mechanisms for broad-spectrum development, adaptive clinical trial designs, intellectual property incentives, manufacturing surge capacity, and international collaboration frameworks. This review demonstrates that broad-spectrum antiviral development has transitioned from theoretical concept to clinical reality, with substantial potential to reduce pandemic morbidity and mortality while minimizing costly confinement measures and enabling rapid first-line defense during the critical early stages of novel pathogen emergence.
Keywords: broad-spectrum antivirals, direct-acting antivirals, host-targeting antivirals, pandemic preparedness, antiviral resistance, viral therapeutics, drug discovery
