Coronaviruses — drug discovery and therapeutic options

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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.

Abstract

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by coronaviruses, have attracted substantial attention owing to their high mortality rates and potential to cause epidemics. Yuen and colleagues discuss progress with treatment options for these syndromes, including virus- and host-targeted drugs, and the challenges that need to be overcome in their further development.

Supplementary information

The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.

Abstract

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.

Supplementary information

The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Alimuddin Zumla:

Bio :

Alimuddin Zumla is professor of infectious diseases and international health in the division of Infection and Immunity at University College London (UCL), UK, a consultant infectious diseases physician at UCL Hospitals NHS Foundation Trust, UK, and a founding director of the University of Zambia–UCL Medical School ( UNZA–UCLMS) Research and Training Programme. He has published over 400 PubMed articles and 21 textbooks. His research has defined the epidemiology and clinical features and improved diagnostics, drug treatment and management protocols of lethal respiratory infectious diseases in Sub-Saharan Africa, the Middle East, the United Kingdom and Europe.

Jasper F. W. Chan:

Bio :

Jasper F. W. Chan is a clinical assistant professor at the State Key Laboratory of Emerging Infectious Diseases, the Carol Yu Centre for Infection, the Research Centre of Infection and Immunology and the Department of Microbiology at the University of Hong Kong (HKU) and is a specialist in clinical microbiology and infection at Queen Mary Hospital in Hong Kong, China, and HKU-Shenzhen Hospital in Shenzhen, China. He received his M.B.B.S. from HKU in 2005 and completed postgraduate specialist training to become a fellow of the Royal College of Physicians (Edinburgh, UK), the Royal College of Pathologists (UK), the Hong Kong College of Pathologists and the Hong Kong Academy of Medicine. He has published over 120 peer-reviewed articles on emerging infectious diseases, particularly those caused by novel coronaviruses.

Esam I. Azhar:

Bio :

Esam I. Azhar is Head of the Special Infectious Agents Unit, and Associate Professor of Medical Virology at the King Fahd Medical Research Centre, Kind Abdul Aziz University, Jeddah, Saudi Arabia. He obtained his M.Sc. and Ph.D. from the University of Sheffield, UK, and is a Fellow of the Royal College of Physicians (Edinburgh, UK). He has published over 70 publications and has made seminal contributions to research on Alkhurma viral haemorrhagic fever, dengue haemorrhagic fever virus, Rift Valley fever virus and Middle East respiratory syndrome coronavirus.

David S. C. Hui:

Bio :

David S. C. Hui is the Stanley Ho Professor of Respiratory Medicine and the Director of the Stanley Ho Centre for Emerging Infectious Diseases at the Chinese University of Hong Kong (CUHK). He graduated from the University of New South Wales, Australia, in 1985, and then trained in Respiratory and Sleep Medicine in Sydney, Australia. He has published well over 240 peer-reviewed journal articles and 23 book chapters since joining the CUHK in 1998. His research interests include the clinical management of severe acute respiratory infections, the safety of respiratory therapy and hospital infection control in the post-SARS (severe acute respiratory syndrome) era.

Kwok-Yung Yuen: kyyuen@hku.hk

Bio :

Kwok-Yung Yuen is the Henry Fok Professor and Chair of Infectious Diseases at The University of Hong Kong (HKU). He also serves as the director of the clinical diagnostic microbiology services at Queen Mary Hospital in Hong Kong, China, and HKU-Shenzhen Hospital in Shenzhen, China, as the co-director of the State Key Laboratory of Emerging Infectious Diseases of China in Hong Kong and as the founding co-director of the HKU-Pasteur Research Centre in Hong Kong. He is an elected Academician of the Chinese Academy of Engineering (Basic Medicine and Health), a founding member of the Academy of Sciences of Hong Kong, and a Fellow of the Royal College of Physicians (London and Edinburgh, UK; as well as Ireland), Royal College of Surgeons (Glasgow, UK) and Royal College of Pathologists (UK). His has published over 800 peer-reviewed articles in the areas of emerging infections and microbial discovery. He and his team have discovered and characterized over 60 novel human and animal viruses, including human coronavirus HKU1 and the bat and human severe acute respiratory syndrome (SARS) coronaviruses.

Journal

Journal ID (nlm-ta): Nat Rev Drug Discov

Journal ID (iso-abbrev): Nat Rev Drug Discov

Title: Nature Reviews. Drug Discovery

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1474-1776

ISSN (Electronic): 1474-1784

Publication date (Electronic): 12 February 2016

Publication date (Print): 2016

Volume: 15

Issue: 5

Pages: 327-347

Affiliations

[1 ]GRID grid.83440.3b, ISNI 0000000121901201, Division of Infection and Immunity, , University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, ; 307 Euston Road, NW1 3AD London UK

[2 ]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

[3 ]GRID grid.412125.1, ISNI 0000 0001 0619 1117, and Medical Laboratory Technology Department, , Special Infectious Agents Unit, King Fahd Medical Research Centre, Faculty of Applied Medical Sciences, King Abdulaziz University, ; P.O. Box 128442, 21362 Jeddah Kingdom of Saudi Arabia

[4 ]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

Article

Publisher ID: BFnrd201537

DOI: 10.1038/nrd.2015.37

PMC ID: 7097181

PubMed ID: 26868298

SO-VID: ce1de37c-2ef7-45d7-8035-3638c577e718

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.