To support urgent research to combat the ongoing outbreak of novel coronavirus 2019-nCoV, the editorial teams at Nature Research have curated a collection of relevant articles. Our collection includes research into the basic biology of coronavirus infection, its detection, treatment and evolution, research into the epidemiology of emerging viral diseases, and our coverage of current events. The articles will remain free to access for as long as the outbreak remains a public health emergency of international concern.
Updates on the respiratory illness that has infected tens of thousands of people.
How science can help control the outbreak
Experts weigh up the best- and worst-case scenarios as the World Health Organization declares a global health emergency.
The strengthening of the Chinese Center for Disease Control and Prevention has been a turning point in outbreak responses in the area. This represents very welcome progress and development for global health security and diplomacy.
As the international community responds to an outbreak of coronavirus-induced pneumonia in Wuhan, China, early and open data sharing — which are vital for its control — depend on the trust that the data will not be used without proper attribution to those who generated it.
Biology of infection and viral structure
Mice made susceptible to MERS-CoV, using CRISPR–Cas9 to alter the gene encoding the dipeptidyl peptidase 4 receptor, allow efficient viral replication in the lungs and display symptoms indicative of severe acute respiratory stress.
Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.
Dampened activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in bat primary immune cells in response to infection with multiple zoonotic viruses is caused by decreased transcriptional priming, the presence of a unique splice variant and an altered leucine-rich repeat domain of bat NLRP3.
SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection
Here, Gassen et al. show that S-phase kinase-associated protein 2 (SKP2) is responsible for lysine-48-linked poly-ubiquitination of beclin 1, resulting in its proteasomal degradation, and that inhibition of SKP2 enhances autophagy and reduces replication of MERS coronavirus.
Structural and functional analyses reveal how 9-O-acetyl sialic acid is recognized by the human coronavirus OC43 S glycoprotein and how this interaction promotes viral entry.
Cryo-EM structures of MERS-CoV S glycoprotein trimer in complex with different sialosides reveal how the virus engages with sialylated receptors, providing insight into receptor specificity and selectivity.
The pathogenic human coronaviruses SARS- and MERS-CoV can cause severe respiratory disease. Here the authors present the 3.1Å cryo-EM structure of the SARS-CoV RNA polymerase nsp12 bound to its essential co-factors nsp7 and nsp8, which is of interest for antiviral drug development.
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
Antibodies that target the N-terminal domain (NTD) of the MERS-CoV spike remain poorly characterized. Here, Zhou et al. report the structural and functional analysis of the NTD-targeting mAb 7D10 and show that it synergizes with antibodies targeting the receptor-binding domain against different MERS-CoV strains.
Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. In this Review, Perng and Lenschow provide new insights into how ISG15 restricts and shapes the host response to viral infection and the viral immune-evasion strategies that counteract ISG15.
Therapeutics and diagnostics
Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV, some of which are already moving into clinical trials.
REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes
A Perspective discussing the factors that have contributed to the success and failure of point-of-care tests for resource-limited settings and the challenges and opportunities that exist for developing new infectious disease diagnostics.
Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.
Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations
Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia. Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ.
Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform
Rachel Graham et al. show that coronaviruses with extensively rewired transcription regulatory networks are effective vaccine candidates against Severe Acute Respiratory Syndrome Coronavirus. The reversion of live-attenuated vaccine strains to virulence can be avoided with these vaccines.
Deubiquitylating enzymes (DUBs) have been implicated in several human diseases, including cancer, neurodegenerative diseases, inflammatory and autoimmune disorders, as well as infectious diseases. Here, Jackson and colleagues discuss the pathological roles of DUBs, consider the challenges in the development of selective DUB inhibitors and highlight first-generation agents approaching clinical trials.
Clinical metagenomic next-generation sequencing (mNGS) is rapidly moving from bench to bedside. This Review discusses the clinical applications of mNGS, including infectious disease diagnostics, microbiome analyses, host response analyses and oncology applications. Moreover, the authors review the challenges that need to be overcome for mNGS to be successfully implemented in the clinical laboratory and propose solutions to maximize the benefits of clinical mNGS for patients.
So-called super-antibodies are highly potent, broadly reactive antiviral antibodies that offer promise for the treatment of various chronic and emerging viruses. This Review describes how recent technological advances led to their isolation from rare, infected individuals and their development for the prevention and treatment of various viral infections.
Epidemiology and evolution
Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.
We need to integrate the knowledge and skills from different disciplines and from communities all over the world to enable effective responses to future epidemics.
The emerging field of precision epidemiology allows the personalized diagnosis, tracking and treatment of infectious diseases.
This Review Article describes how recent advances in viral genome sequencing and phylogenetics have enabled key issues associated with outbreak epidemiology to be more accurately addressed, and highlights the requirements and challenges for generating, sharing and using such data when tackling a viral outbreak.
Emerging viral diseases present a huge and increasingly important global threat to public health systems. Graham and Sullivan discuss the challenges presented by emerging viral diseases and discuss how innovations in technology and policy can address this threat.
Zoonotic diseases present a substantial global health burden. In this Opinion article, Plowrightet al. present an integrative conceptual and quantitative model that reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans.
Next-generation sequencing has the potential to support public health surveillance systems to improve the early detection of emerging infectious diseases. This Review delineates the role of genomics in rapid outbreak response and the challenges that need to be tackled for genomics-informed pathogen surveillance to become a global reality.
The virulence of viruses is a major determinant of the health burden of viral infections in humans and other species. In this article, Geoghegan and Holmes discuss how largely disparate research fields — theoretical modelling of virulence evolution and experimental dissection of genetic virulence determinants in laboratory model systems — can be bridged by considering real genomic data of viral evolution in a phylogenetic context. They describe the underlying principles of virulence evolution and how they apply to real-world viral infections and outbreaks of global importance.
Analysis of viral samples from deceased piglets shows that a bat coronavirus was responsible for an outbreak of fatal disease in China and highlights the importance of the identification of coronavirus diversity and distribution in bats in order to mitigate future outbreaks of disease.
Understanding global epidemics spread is crucial for preparedness and response. Here the authors introduce an analytical framework to study epidemic spread on air transport networks, and demonstrate its power to estimate key epidemic parameters by application to the recent influenza pandemic and Ebola outbreak.