In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious
virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral
species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern
medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use
of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from
the human population. Unfortunately, several viral species maintain a significant ability to mutate and “escape” vaccine-induced immune
responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in
the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate
anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in
the design and synthesis of viral protease inhibitors.
Keywords: Viral proteases, protease inhibitors, HIV-1, HCV, Flaviviridae, SARS, Herpesviridae, Adenoviridae.
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