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Despite ongoing efforts to develop effective, low\u2010toxicity 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\u2010resistant 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\u2010efficient 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\u2010aided drug design, artificial intelligence and machine learning, gene\u2010editing technologies, drug combination therapy and nanotechnology\u2010enhanced drug delivery systems. Additionally, this study proposes a simple decision\u2010focused 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.<\/jats:p>","DOI":"10.1111\/cbdd.70365","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:16:19Z","timestamp":1784862979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancing Antiviral Design: Integrating Natural Products, Computation and Targeted Delivery"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6093-8090","authenticated-orcid":false,"given":"Adedayo Ayodeji","family":"Lanrewaju","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Science Durban University of Technology  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-1465","authenticated-orcid":false,"given":"Abimbola Motunrayo","family":"Folami","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Science Durban University of Technology  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-9220","authenticated-orcid":false,"given":"Saheed","family":"Sabiu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Science Durban University of Technology  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feroz Mahomed","family":"Swalaha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Science Durban University of Technology  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24049"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2019.1635009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2022.107766"},{"key":"e_1_2_11_6_1","first-page":"285","volume-title":"Integration of Pharmaceutical Discovery and Development: Case Histories","author":"Adams W. 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