Viral infections can range from mild, self-limited illnesses to severe, life-threatening diseases. In an era of increased global interdependence, forced migration, and intensified globalization, the rapid replication and high contagion rates of viruses have become a critical concern. The resurgence of infections once believed to be under control, driven by viral genetic mutations and anti-vaccine movements, has further heightened the threat of deadly pandemics. To combat this global health crisis, there has been a renewed focus on drug development strategies. The World Health Organization (WHO) has emphasized the challenge posed by limited resources for disease research and development, particularly given the vast array of potential pathogens. To address this, the WHO has established a prioritized list of diseases with the greatest public health impact, based on their epidemic potential and the lack of effective countermeasures. This list is further detailed by the WHO's document "Pathogens Prioritization" which outlines the viral families and their respective members considering the risk of causing Public Health Emergencies of International Concern (PHEICs) or a pandemic (Table ). Despite ongoing efforts, developing effective antivirals for most viruses remains a significant challenge due to several key obstacles in antiviral discovery. These include the identification of specific targets, narrow treatment windows, and the emergence of mutations that contribute to antiviral resistance. In response, there has been a growing focus on developing structurally diverse antivirals with enhanced safety profiles, as well as those that retain efficacy against drug-resistant strains. This shift in focus has led to renewed interest in compounds with novel mechanisms of action. Acute respiratory disease (ARD) represents a significant portion of acute illnesses and fatalities worldwide. Acute viral respiratory tract infections alone are responsible for approximately 80% of ARD cases. Key viral pathogens in this category include influenza, respiratory syncytial virus (RSV), coronaviruses, adenovirus, and rhinovirus, all of which are related with some of the most highlighted disease on the WHO's prioritized list (Table ). While viruses like adenovirus and rhinovirus typically result in lower mortality rates, they contribute substantially to morbidity and place a significant economic burden on healthcare systems. 10 Computer-aided drug design (CADD) has significantly advanced antiviral discovery. Liao et al. identified five natural compounds -narcissoside, kaempferol-3-O-gentiobioside, rutin, vicin-2, and isoschaftoside-as potential SARS-CoV-2 Mpro inhibitors. Generative topographic mapping (GTM) has aided in identifying antiviral motifs and screening virtual chemical libraries, as demonstrated in the design of anti-herpes compounds (Herpes simplex virus type 1). CADD methods have also identified several promising antiviral compounds. These include baricitinib, galidesivir, and molnupiravir. Baricitinib was predicted by artificial intelligence (AI)-driven analysis to inhibit viral entry and inflammation in SARS-CoV-2. Galidesivir, an antiviral for Ebola and Zika, was evaluated through structural modeling as a potential inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Molnupiravir (EIDD-2801), a prodrug of β-D-N4-hydroxycytidine, was optimized through docking and molecular dynamics to interfere with SARS-CoV-2 replication (Fig. ). Approved antivirals such as remdesivir, favipiravir, and ritonavir have been repurposed for respiratory viruses through virtual screening (VS), further confirming their potential to inhibit RNA polymerases (Fig. ).