SrasV1, PubMed, Curation, bibRecord, 000E87

Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus.

Identifieur interne : 000E87 ( PubMed/Curation ); précédent : 000E86; suivant : 000E88

Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus.

Auteurs : Kai-Wen Cheng [Taïwan] ; Shu-Chun Cheng [Taïwan] ; Wei-Yi Chen [Taïwan] ; Min-Han Lin [Taïwan] ; Shang-Ju Chuang [Taïwan] ; I-Hsin Cheng [Taïwan] ; Chiao-Yin Sun [Taïwan] ; Chi-Yuan Chou [Taïwan]

Source :

Antiviral research [ 1872-9096 ] ; 2015.

RBID : pubmed:25542975

Descripteurs français

KwdFr :
- Acide mycophénolique (pharmacologie), Antiviraux (pharmacologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie), Cysteine endopeptidases, Cysteine proteases (), Cysteine proteases (métabolisme), Inhibiteurs de la cystéine protéinase (pharmacologie), Modèles moléculaires, Protéines virales (antagonistes et inhibiteurs), Synergie des médicaments, Tioguanine (pharmacologie), Virus du SRAS (), Virus du SRAS (enzymologie).
MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Virus du SRAS.
- métabolisme : Cysteine proteases.
- pharmacologie : Acide mycophénolique, Antiviraux, Inhibiteurs de la cystéine protéinase, Tioguanine.
- Coronavirus du syndrome respiratoire du Moyen-Orient, Cysteine endopeptidases, Cysteine proteases, Modèles moléculaires, Synergie des médicaments, Virus du SRAS.

English descriptors

KwdEn :
- Antiviral Agents (pharmacology), Cysteine Endopeptidases, Cysteine Proteases (chemistry), Cysteine Proteases (metabolism), Cysteine Proteinase Inhibitors (pharmacology), Drug Synergism, Mercaptopurine (pharmacology), Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (enzymology), Models, Molecular, Mycophenolic Acid (pharmacology), SARS Virus (drug effects), SARS Virus (enzymology), Thioguanine (pharmacology), Viral Proteins (antagonists & inhibitors).
MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Cysteine Proteases.
- chemical , metabolism : Cysteine Proteases.
- chemical , pharmacology : Antiviral Agents, Cysteine Proteinase Inhibitors, Mercaptopurine, Mycophenolic Acid, Thioguanine.
- chemical : Cysteine Endopeptidases.
- drug effects : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- enzymology : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- Drug Synergism, Models, Molecular.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PL(pro)) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PL(pro) inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PL(pro). Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PL(pro) and these can now be used as lead compounds for further antiviral drug development.

DOI: 10.1016/j.antiviral.2014.12.011
PubMed: 25542975

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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PL(pro)) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PL(pro) inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PL(pro). Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PL(pro) and these can now be used as lead compounds for further antiviral drug development. </div>
</front>
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<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PL(pro)) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PL(pro) inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PL(pro). Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PL(pro) and these can now be used as lead compounds for further antiviral drug development. </AbstractText>
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Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus.

Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus.

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