Drug design targeting the main protease, the Achilles' heel of coronaviruses.
Coronaviruses (CoVs), a genus containing about 26 known species to date, cause highly prevalent diseases and are often severe or fatal in humans and animals. In 2003, a previously unknown coronavirus was identified to be the etiological agent of a global outbreak of a form of life-threatening pneumonia called severe acute respiratory syndrome (SARS). No efficacious therapy is currently available, and vaccines and drugs are under development to prevent SARS-CoV infection in many countries. The CoV main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, is an attractive target for drug design. This review summarizes the recent advances in biological and structural studies, together with development of inhibitors targeting CoV M(pro)s. It is expected that inhibitors targeting CoV M(pro)s could be developed into wide-spectrum antiviral drugs against existing and possible future emerging CoV-associated diseases.
Yang
Haitao
H
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Bartlam
Mark
M
Rao
Zihe
Z
D000595:Amino Acid Sequence; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D017076:Computer-Aided Design; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology; D064370:Spike Glycoprotein, Coronavirus; D013379:Substrate Specificity; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D011480:Protease Inhibitors; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases