PDBsum entry 5y3e

Hydrolase

PDB id: 5y3e

Contents

Protein chain

317 a.a.

Ligands

GOL ×3

Metals

_ZN

_NA ×5

Waters ×214

References listed in PDB file

Key reference

• Title: Disulfiram can inhibit mers and sars coronavirus papain-Like proteases via different modes.
• Authors: M.H.Lin, D.C.Moses, C.H.Hsieh, S.C.Cheng, Y.H.Chen, C.Y.Sun, C.Y.Chou.
• Ref.: Antiviral Res, 2018, 150, 155-163. [DOI no: 10.1016/j.antiviral.2017.12.015]
• PubMed id: 29289665

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 (PL^pros) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PL^probut as a competitive (or mixed) inhibitor of SARS-CoV PL^pro. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL^proby disulfiram, while synergistic inhibition of MERS-CoV PL^proby disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.