Academic Editor: Sang Heui Seo
2020 and 2021 were disastrous years across the world, with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) virus as a pandemic, which continues to be a top global health issue. There are still many countries and regions struggling to fight coronavirus disease 2019 (COVID-19), and, with the emergence of the various variants of the virus, we are still far from considering this global pandemic over. In addition to having good diagnostic tools and a variety of vaccines with high efficacy, it is of utmost importance to develop effective antiviral drugs or therapies to battle COVID-19. Aptamers known as the next-generation targeting elements can offer promising opportunities in developing antiviral drugs against SARS-CoV-2. This is owing to their high specificity and affinity, making them ideal for targeting ligands and neutralizers to impede both, viral entry and replication or even further enhance the anti-infection effects in the infected host cells. Also, aptamers are extremely attractive as they can be rapidly synthesized and scalable with a lower production cost. This work provides in-depth discussions on the potential of aptamers in therapeutic applications, their mode of action, and current progress on the use of aptamer-based therapies against SARS-CoV-2 and other viruses. The article also discusses the limitations associated with aptamer-based SARS-CoV-2-antiviral therapy with several proposed ideas to resolve them. Lastly, theranostic applications of aptamer nanoformulated dendrimers against viral infections are discussed.