A novel coronavirus has resulted in an ongoing outbreak of viral pneumonia in China.^1-3 Person-to-person transmission has been demonstrated,¹ but, to our knowledge, transmission of the novel coronavirus that causes coronavirus disease 2019 (COVID-19) from an asymptomatic carrier with normal chest computed tomography (CT) findings has not been reported.

Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted.

The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 million deaths. Early virus-mediated immune suppression is believed to be one of the unique characteristics of SARS-CoV-2 infection and contributes at least partially to the viral pathogenesis. In this study, we identified the key viral interferon antagonists of SARS-CoV-2 and compared them with two well-characterized SARS-CoV interferon antagonists, PLpro and orf6. Here we demonstrated that the SARS-CoV-2 nsp13, nsp14, nsp15 and orf6, but not the unique orf8, could potently suppress primary interferon production and interferon signalling. Although SARS-CoV PLpro has been well-characterized for its potent interferon-antagonizing, deubiquitinase and protease activities, SARS-CoV-2 PLpro, despite sharing high amino acid sequence similarity with SARS-CoV, loses both interferon-antagonising and deubiquitinase activities. Among the 27 viral proteins, SARS-CoV-2 orf6 demonstrated the strongest suppression on both primary interferon production and interferon signalling. Orf6-deleted SARS-CoV-2 may be considered for the development of intranasal live-but-attenuated vaccine against COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

Severe acute respiratory syndrome Coronavirus (SARS‐CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS‐CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor‐associated factor 3 (TRAF3)–mediated ubiquitination of apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC). SARS‐CoV and its ORF3a protein were found to be potent activators of pro–IL‐1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro–IL‐1β transcription through activation of NF‐κB, which was mediated by TRAF3‐dependent ubiquitination and processing of p105. ORF3a‐induced elevation of IL‐1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3‐dependent K63‐linked ubiquitination of ASC was more pronounced in SARS‐CoV–infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS‐CoV ORF3a protein activates NF‐κB and the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of p105 and ASC.—Siu, K.‐L., Yuen, K.‐S., Castano‐Rodriguez, C., Ye, Z.‐W., Yeung, M.‐L., Fung, S.‐Y., Yuan, S., Chan, C.‐P., Yuen, K.‐Y., Enjuanes, L., Jin, D.‐Y. Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC. FASEB J. 33, 8865–8877 (2019). www.fasebj.org