PT  - JOURNAL ARTICLE
AU  - Wei Zhu
AU  - Zeenat A Shyr
AU  - Donald C. Lo
AU  - Wei Zheng
TI  - <strong>Viral Proteases as Targets for COVID-19 Drug Development</strong>
AID  - 10.1124/jpet.121.000688
DP  - 2021 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - JPET-MR-2021-000688
4099  - http://jpet.aspetjournals.org/content/early/2021/05/10/jpet.121.000688.short
4100  - http://jpet.aspetjournals.org/content/early/2021/05/10/jpet.121.000688.full
AB  - Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global threat since its emergence. Although several COVID-19 vaccines have become available, the prospective timeframe for achieving effective levels of vaccination across global populations remains uncertain. Moreover, the emergence of SARS-CoV-2 variants presents continuing potential challenges for future vaccination planning. Therefore, development of effective antiviral therapies continues to be an urgent unmet need for COVID-19. Successful antiviral regimens for the treatment of human immunodeficiency virus and hepatitis C virus infections have established viral proteases as validated targets for antiviral drug development. In this context, we review here protease targets in drug development, currently available antiviral protease inhibitors, and therapeutic development efforts on SARS-CoV-2 main protease and papain-like protease. Significance Statement Coronavirus disease 2019 (COVID-19) continues to be a global threat since its emergence. The development of effective antiviral therapeutics for COVID-19 remains an urgent and long-term need. Because viral proteases are validated drug targets, specific SARS-CoV-2 protease inhibitors are critical therapeutics to be developed for treatment of COVID-19.