SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes

Shi, Chong-Shan; Nabar, Neel R.; Huang, Ning‐Na; Kehrl, John H.

doi:10.1038/s41420-019-0181-7

Cited by 398 publications

(403 citation statements)

References 48 publications

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“…As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or (Figure 5(B)) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes [26], but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure prediction, this novel orf8 has a high possibility to form a protein with an alpha-helix, following with a betasheet(s) containing six strands ( Figure 5(C)).…”

Section: Hku-sz-005bmentioning

confidence: 99%

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Chan

Kok

Zhu

et al. 2020

Emerging Microbes & Infections

2,786

2,895

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A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

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Section: Hku-sz-005bmentioning

confidence: 99%

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Chan

Kok

Zhu

et al. 2020

Emerging Microbes & Infections

2,786

2,895

View full text Add to dashboard Cite

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“…Orf8 protein of SARS-CoV-2 doesn't contain a known useful motif or region. A total motif VLVVL (amino corrosive 75-79) has been found in SARS-CoV orf8b which was appeared to trigger intracellular stress pathways and enact NOD-like receptor family pyrin region containing-3 (NLRP3) (Shi et al, 2019). Moreover, multiple arrangements with different coronavirus ORF8 sequences propose that L84 related to 28144T > C (L84S) isn't preserved (Koyama et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of a novel SARS-CoV-2

2020

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“…Orf8 protein of SARS-CoV-2 does not contain known functional domain or motif. An aggregation motif VLVVL (amino acid 75-79) has been found in SARS-CoV orf8b which was shown to trigger intracellular stress pathways and activate NOD-like receptor family pyrin domain-containing-3 (NLRP3) inflammasomes [90]. Therefore, it will be clinically meaningful to analyze the biological function of these two specific proteins (orf8 and orf10) in SARS-CoV-2.…”

Section: Proteomic Comparisonmentioning

confidence: 99%

Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV

Zhao

Teng

et al. 2020

Viruses

641

622

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After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as "coronavirus disease 2019" (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

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SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes

Cited by 398 publications

References 48 publications

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Genomic characterization of a novel SARS-CoV-2

Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV

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