Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.
Antiviral Res
; 150: 155-163, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-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 (PLpros) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PLpro but as a competitive (or mixed) inhibitor of SARS-CoV PLpro. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PLpro by disulfiram, while synergistic inhibition of MERS-CoV PLpro by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Peptídeo Hidrolases
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Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
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Dissulfiram
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Coronavírus da Síndrome Respiratória do Oriente Médio
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article