Antiviral Drug Discovery Against SARS-CoV

Yu-Shan      Wu; Wen-Hsing      Lin; John      T.-A.Hsu; Hsing-Pang      Hsieh

Abstract

Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARSCoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV Mpro; 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

Keywords: Severe Acute Respiratory Syndrome (SARS), CPE Inhibition Assays, Virtual Screening, Replicon RNA Systems, Lead Optimization, Helicase Inhibitor, RNA-dependent RNA polymerase (RdRp) Inhibitor

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