Advancing Antiviral Design: Integrating Natural Products, Computation and Targeted Delivery.

The COVID-19 pandemic highlighted the role of rapid viral mutation and global connectivity in accelerating viral emergence and spread, emphasising the necessity for expedited and adaptable antiviral drug discovery and development. Despite ongoing efforts to develop effective, low-toxicity therapeutics, the number of antivirals that have achieved clinical approval remains limited. The shortfall is especially significant in developing countries, where access to new antivirals is limited by high prices, few options, import dependence, unstable supply chains and weak purchasing systems. The challenge is further heightened by the emergence of increasingly drug-resistant variants while vaccines often provide inadequate protection against newly mutated or novel viruses. Consequently, the identification of novel antiviral agents that are both effective and cost-efficient via innovative strategies for antiviral drug discovery is essential to manage and control viral infections. Therefore, this review examines the different challenges associated with conventional antiviral drugs alongside recent strategies in antiviral drug discovery and development, such as the exploitation of plant secondary metabolites with antiviral properties, advanced microscopy technologies, computer-aided drug design, artificial intelligence and machine learning, gene-editing technologies, drug combination therapy and nanotechnology-enhanced drug delivery systems. Additionally, this study proposes a simple decision-focused pathway integrating natural products, computation and targeted delivery to guide candidate prioritisation, optimisation and translation from discovery to implementation. While these emerging strategies offer considerable promise, challenges related to validation, toxicity, scalability and equitable access remain important considerations for successful clinical translation. Future research should therefore integrate complementary technologies to accelerate the development of effective antiviral agents against current and emerging viral threats.