5Y3Q

Crystal structure of SARS coronavirus papain-like protease conjugated with beta-mercaptoethanol

Summary for 5Y3Q

• Entry DOI: 10.2210/pdb5y3q/pdb
• Descriptor: Replicase polyprotein 1a, ZINC ION, BETA-MERCAPTOETHANOL, ... (6 entities in total)
• Functional Keywords: complex structure, hydrolase
• Biological source: Human SARS coronavirus (SARS-CoV)
• Cellular location: Non-structural protein 3: Host membrane ; Multi-pass membrane protein . Non-structural protein 4: Host membrane ; Multi-pass membrane protein . Non-structural protein 6: Host membrane ; Multi-pass membrane protein . Non-structural protein 7: Host cytoplasm, host perinuclear region . Non-structural protein 8: Host cytoplasm, host perinuclear region . Non-structural protein 9: Host cytoplasm, host perinuclear region . Non-structural protein 10: Host cytoplasm, host perinuclear region : P0C6U8
• Total number of polymer chains: 1
• Total formula weight: 36904.91

Authors

Lin, M.H.,Chou, C.Y. (deposition date: 2017-07-29, release date: 2018-01-10, Last modification date: 2023-11-22)

Primary citation

Lin, M.H.,Moses, D.C.,Hsieh, C.H.,Cheng, S.C.,Chen, Y.H.,Sun, C.Y.,Chou, C.Y.
Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes
Antiviral Res., 150:155-163, 2017

PubMed Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in southern China in late 2002 and caused a global outbreak with a fatality rate around 10% in 2003. Ten years later, a second highly pathogenic human CoV, MERS-CoV, emerged in the Middle East and has spread to other countries in Europe, North Africa, North America and Asia. As of November 2017, MERS-CoV had infected at least 2102 people with a fatality rate of about 35% globally, and hence there is an urgent need to identify antiviral drugs that are active against MERS-CoV. Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PLs) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PL but as a competitive (or mixed) inhibitor of SARS-CoV PL. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL by disulfiram, while synergistic inhibition of MERS-CoV PL by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.

PubMed: 29289665
DOI: 10.1016/j.antiviral.2017.12.015

Experimental method

X-RAY DIFFRACTION (1.65 Å)