Antiviral drug discovery against SARS-CoV.
Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. 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 M(pro); 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.
Wu
Yu-Shan
YS
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town. Miaoli County 350, Taiwan.
Lin
Wen-Hsing
WH
Hsu
John T-A
JT
Hsieh
Hsing-Pang
HP
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010455:Peptides / Q000032:analysis; D011480:Protease Inhibitors / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000037:antagonists & inhibitors
D000998:Antiviral Agents; D010455:Peptides; D011480:Protease Inhibitors; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases