Coronaviruses — drug discovery and therapeutic options
Identifieur interne : 002B99 ( Ncbi/Merge ); précédent : 002B98; suivant : 002C00Coronaviruses — drug discovery and therapeutic options
Auteurs : Alimuddin Zumla ; Jasper F. W. Chan ; Esam I. Azhar ; David S. C. Hui [Hong Kong] ; Kwok-Yung YuenSource :
- Nature Reviews. Drug Discovery [ 1474-1776 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
- traitement médicamenteux : Infections de l'appareil respiratoire.
- usage thérapeutique : Antiviraux.
- virologie : Infections de l'appareil respiratoire.
- Coronavirus, Découverte de médicament, Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Antiviral Agents.
- classification : Coronavirus.
- drug effects : Coronavirus.
- drug therapy : Respiratory Tract Infections.
- virology : Respiratory Tract Infections.
- Drug Discovery, Humans.
Abstract
Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are examples of emerging zoonotic coronavirus infections capable of person-to-person transmission that result in large-scale epidemics with substantial effects on patient health and socioeconomic factors. Unlike patients with mild illnesses that are caused by other human-pathogenic coronaviruses, patients with SARS or MERS coronavirus infections may develop severe acute respiratory disease with multi-organ failure. The case–fatality rates of SARS and MERS are approximately 10% and 35%, respectively. Both SARS and MERS pose major clinical management challenges because there is no specific antiviral treatment that has been proven to be effective in randomized clinical trials for either infection. Substantial efforts are underway to discover new therapeutic agents for coronavirus infections. Virus-based therapies include monoclonal antibodies and antiviral peptides that target the viral spike glycoprotein, viral enzyme inhibitors, viral nucleic acid synthesis inhibitors and inhibitors of other viral structural and accessory proteins. Host-based therapies include agents that potentiate the interferon response or affect either host signalling pathways involved in viral replication or host factors utilized by coronaviruses for viral replication. The major challenges in the clinical development of novel anti-coronavirus drugs include the limited number of suitable animal models for the evaluation of potential treatments for SARS and MERS, the current absence of new SARS cases, the limited number of MERS cases — which are also predominantly geographically confined to the Middle East — as well as the lack of industrial incentives to develop antivirals for mild infections caused by other, less pathogenic coronaviruses. The continuing threat of MERS-CoV to global health 3 years after its discovery presents a golden opportunity to tackle current obstacles in the development of new anti-coronavirus drugs. A well-organized, multidisciplinary, international collaborative network consisting of clinicians, virologists and drug developers, coupled to political commitment, should be formed to carry out clinical trials using anti-coronavirus drugs that have already been shown to be safe and effective
The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/nrd.2015.37
PubMed: 26868298
PubMed Central: 7097181
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<front><div type="abstract" xml:lang="en"><title>Key Points</title>
<p id="Par6"><list list-type="bullet"><list-item><p id="Par7">Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are examples of emerging zoonotic coronavirus infections capable of person-to-person transmission that result in large-scale epidemics with substantial effects on patient health and socioeconomic factors. Unlike patients with mild illnesses that are caused by other human-pathogenic coronaviruses, patients with SARS or MERS coronavirus infections may develop severe acute respiratory disease with multi-organ failure. The case–fatality rates of SARS and MERS are approximately 10% and 35%, respectively.</p>
</list-item>
<list-item><p id="Par8">Both SARS and MERS pose major clinical management challenges because there is no specific antiviral treatment that has been proven to be effective in randomized clinical trials for either infection. Substantial efforts are underway to discover new therapeutic agents for coronavirus infections.</p>
</list-item>
<list-item><p id="Par9">Virus-based therapies include monoclonal antibodies and antiviral peptides that target the viral spike glycoprotein, viral enzyme inhibitors, viral nucleic acid synthesis inhibitors and inhibitors of other viral structural and accessory proteins.</p>
</list-item>
<list-item><p id="Par10">Host-based therapies include agents that potentiate the interferon response or affect either host signalling pathways involved in viral replication or host factors utilized by coronaviruses for viral replication.</p>
</list-item>
<list-item><p id="Par11">The major challenges in the clinical development of novel anti-coronavirus drugs include the limited number of suitable animal models for the evaluation of potential treatments for SARS and MERS, the current absence of new SARS cases, the limited number of MERS cases — which are also predominantly geographically confined to the Middle East — as well as the lack of industrial incentives to develop antivirals for mild infections caused by other, less pathogenic coronaviruses.</p>
</list-item>
<list-item><p id="Par12">The continuing threat of MERS-CoV to global health 3 years after its discovery presents a golden opportunity to tackle current obstacles in the development of new anti-coronavirus drugs. A well-organized, multidisciplinary, international collaborative network consisting of clinicians, virologists and drug developers, coupled to political commitment, should be formed to carry out clinical trials using anti-coronavirus drugs that have already been shown to be safe and effective <italic>in vitro</italic>
and/or in animal models, particularly lopinavir–ritonavir, interferon beta-1b and monoclonal antibodies and antiviral peptides targeting the viral spike glycoprotein.</p>
</list-item>
</list>
</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<double pmid="26868298"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Coronaviruses — drug discovery and therapeutic options</title>
<author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.83440.3b</institution-id>
<institution-id institution-id-type="ISNI">0000000121901201</institution-id>
<institution>Division of Infection and Immunity,</institution>
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</institution-wrap>
307 Euston Road, NW1 3AD London UK</nlm:aff>
<wicri:noCountry code="subfield">NW1 3AD London UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F. W." last="Chan">Jasper F. W. Chan</name>
<affiliation><nlm:aff id="Aff2">Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Research Centre of Infection and Immunology, University Pathology Building, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region of the People's Republic of China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong Special Administrative Region of the People's Republic of China</wicri:noCountry>
</affiliation>
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<author><name sortKey="Azhar, Esam I" sort="Azhar, Esam I" uniqKey="Azhar E" first="Esam I." last="Azhar">Esam I. Azhar</name>
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<institution>Special Infectious Agents Unit, King Fahd Medical Research Centre, Faculty of Applied Medical Sciences, King Abdulaziz University,</institution>
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P.O. Box 128442, 21362 Jeddah Kingdom of Saudi Arabia</nlm:aff>
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</author>
<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S. C." last="Hui">David S. C. Hui</name>
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<orgName type="university">Université chinoise de Hong Kong</orgName>
<country>Hong Kong</country>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation><nlm:aff id="Aff2">Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Research Centre of Infection and Immunology, University Pathology Building, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region of the People's Republic of China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong Special Administrative Region of the People's Republic of China</wicri:noCountry>
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<idno type="doi">10.1038/nrd.2015.37</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Coronaviruses — drug discovery and therapeutic options</title>
<author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.83440.3b</institution-id>
<institution-id institution-id-type="ISNI">0000000121901201</institution-id>
<institution>Division of Infection and Immunity,</institution>
<institution>University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust,</institution>
</institution-wrap>
307 Euston Road, NW1 3AD London UK</nlm:aff>
<wicri:noCountry code="subfield">NW1 3AD London UK</wicri:noCountry>
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<affiliation><nlm:aff id="Aff2">Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Research Centre of Infection and Immunology, University Pathology Building, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region of the People's Republic of China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong Special Administrative Region of the People's Republic of China</wicri:noCountry>
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<institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id>
<institution>and Medical Laboratory Technology Department,</institution>
<institution>Special Infectious Agents Unit, King Fahd Medical Research Centre, Faculty of Applied Medical Sciences, King Abdulaziz University,</institution>
</institution-wrap>
P.O. Box 128442, 21362 Jeddah Kingdom of Saudi Arabia</nlm:aff>
<wicri:noCountry code="subfield">21362 Jeddah Kingdom of Saudi Arabia</wicri:noCountry>
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<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S. C." last="Hui">David S. C. Hui</name>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Division of Respiratory Medicine and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, New Territories Hong Kong Special Administrative Region of the People's Republic of China</nlm:aff>
<orgName type="university">Université chinoise de Hong Kong</orgName>
<country>Hong Kong</country>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation><nlm:aff id="Aff2">Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Research Centre of Infection and Immunology, University Pathology Building, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region of the People's Republic of China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong Special Administrative Region of the People's Republic of China</wicri:noCountry>
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</analytic>
<series><title level="j">Nature Reviews. Drug Discovery</title>
<idno type="ISSN">1474-1776</idno>
<idno type="eISSN">1474-1784</idno>
<imprint><date when="2016">2016</date>
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<front><div type="abstract" xml:lang="en"><title>Key Points</title>
<p id="Par6"><list list-type="bullet"><list-item><p id="Par7">Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are examples of emerging zoonotic coronavirus infections capable of person-to-person transmission that result in large-scale epidemics with substantial effects on patient health and socioeconomic factors. Unlike patients with mild illnesses that are caused by other human-pathogenic coronaviruses, patients with SARS or MERS coronavirus infections may develop severe acute respiratory disease with multi-organ failure. The case–fatality rates of SARS and MERS are approximately 10% and 35%, respectively.</p>
</list-item>
<list-item><p id="Par8">Both SARS and MERS pose major clinical management challenges because there is no specific antiviral treatment that has been proven to be effective in randomized clinical trials for either infection. Substantial efforts are underway to discover new therapeutic agents for coronavirus infections.</p>
</list-item>
<list-item><p id="Par9">Virus-based therapies include monoclonal antibodies and antiviral peptides that target the viral spike glycoprotein, viral enzyme inhibitors, viral nucleic acid synthesis inhibitors and inhibitors of other viral structural and accessory proteins.</p>
</list-item>
<list-item><p id="Par10">Host-based therapies include agents that potentiate the interferon response or affect either host signalling pathways involved in viral replication or host factors utilized by coronaviruses for viral replication.</p>
</list-item>
<list-item><p id="Par11">The major challenges in the clinical development of novel anti-coronavirus drugs include the limited number of suitable animal models for the evaluation of potential treatments for SARS and MERS, the current absence of new SARS cases, the limited number of MERS cases — which are also predominantly geographically confined to the Middle East — as well as the lack of industrial incentives to develop antivirals for mild infections caused by other, less pathogenic coronaviruses.</p>
</list-item>
<list-item><p id="Par12">The continuing threat of MERS-CoV to global health 3 years after its discovery presents a golden opportunity to tackle current obstacles in the development of new anti-coronavirus drugs. A well-organized, multidisciplinary, international collaborative network consisting of clinicians, virologists and drug developers, coupled to political commitment, should be formed to carry out clinical trials using anti-coronavirus drugs that have already been shown to be safe and effective <italic>in vitro</italic>
and/or in animal models, particularly lopinavir–ritonavir, interferon beta-1b and monoclonal antibodies and antiviral peptides targeting the viral spike glycoprotein.</p>
</list-item>
</list>
</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S C" last="Hui">David S C. Hui</name>
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<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S C" last="Hui">David S C. Hui</name>
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<series><title level="j">Nature reviews. Drug discovery</title>
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<term>Humans</term>
<term>Respiratory Tract Infections (drug therapy)</term>
<term>Respiratory Tract Infections (virology)</term>
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<term>Coronavirus ()</term>
<term>Découverte de médicament</term>
<term>Humains</term>
<term>Infections de l'appareil respiratoire (traitement médicamenteux)</term>
<term>Infections de l'appareil respiratoire (virologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term>
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<keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Respiratory Tract Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections de l'appareil respiratoire</term>
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<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections de l'appareil respiratoire</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Respiratory Tract Infections</term>
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<keywords scheme="MESH" xml:lang="en"><term>Drug Discovery</term>
<term>Humans</term>
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<front><div type="abstract" xml:lang="en">In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.</div>
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