Antiviral Drug Design: Past, Presence, and Future

Viral infectious diseases represent a major global health burden, contributing significantly to morbidity and mortality across diverse populations. Lower respiratory infections, including bronchitis, bronchiolitis, and pneumonia, accounted for more than 2 million deaths worldwide in both 2016 and 2019, while upper respiratory tract infections such as the common cold, sinusitis, and pharyngitis collectively caused billions of incident cases with notable mortality. Gastrointestinal viruses, particularly rotaviruses, remain a leading cause of severe pediatric gastroenteritis, resulting in thousands of childhood deaths daily, especially in developing countries. Exanthematous viral diseases, including measles and rubella, continue to pose high transmission risks, with measles alone responsible for over half a million child deaths annually. Hepatic viral infections, most notably hepatitis viruses A-E, affect more than two billion individuals globally and cause approximately 1.4 million deaths each year. Cutaneous viral diseases, hemorrhagic fevers, and neurologic infections such as polio and viral encephalitis further illustrate the broad clinical spectrum and public health challenges posed by viral pathogens. Addressing these threats relies heavily on the development and application of antiviral agents with diverse mechanisms of action. These include direct virus-targeting approaches-such as attachment, entry, uncoating, protease, polymerase, and integrase inhibitors-as well as reverse transcriptase inhibitors used in HIV management. Complementary strategies involve indirect virus-targeting antivirals that disrupt host cellular pathways exploited during viral replication. Together, these therapeutic strategies highlight the critical need for continued innovation and comprehensive antiviral development to mitigate the ongoing global burden of viral diseases.