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Coronaviruses — drug discovery and therapeutic options

Identifieur interne : 001059 ( Main/Exploration ); précédent : 001058; suivant : 001060

Coronaviruses — drug discovery and therapeutic options

Auteurs : Alimuddin Zumla ; Jasper F. W. Chan ; Esam I. Azhar ; David S. C. Hui [Hong Kong] ; Kwok-Yung Yuen

Source :

RBID : PMC:7097181

Descripteurs français

English descriptors

Abstract

Key Points

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 in vitro and/or in animal models, particularly lopinavir–ritonavir, interferon beta-1b and monoclonal antibodies and antiviral peptides targeting the viral spike glycoprotein.

Supplementary information

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


Affiliations:


Links toward previous steps (curation, corpus...)


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<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>
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<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>
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