Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism

Lee, Yoo‐Hyun; Kim, Seong Jun; Myoung, Jinjong

doi:10.4014/jmb.1911.11024

Cited by 11 publications

(9 citation statements)

References 57 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The precise role of IFNs in SARS-CoV-2 infection is yet unclear and requires further investigation. It is unclear whether patients by default produce amounts of interferon like certain mammals ( 87 ) or low IFN concentrations may reflect the coronaviruses’ capacity to prevent/reduce its production and action ( 88 – 95 ). The latter may be plausible given that CoV are well capable of preventing NF-κB activation ( 96 ) and protein translation ( 97 ).…”

Section: Immunopathogenesis Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities

Osuchowski

Aletti

Cavaillon

et al. 2020

Shock

View full text Add to dashboard Cite

Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by Coronavirus Disease 2019 (COVID-19) and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. The capacity for rapid information dissemination has emerged as a double-edged sword; the existing gap of high-quality data is frequently filled by anecdotal reports, contradictory statements, and misinformation. This review addresses several important aspects unique to the SARS-CoV-2/COVID-19 pandemic highlighting the most relevant knowledge gaps and existing windows-of-opportunity. Specifically, focus is given on SARS-CoV-2 immunopathogenesis in the context of experimental therapies and preclinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring, and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks, and regulatory partnerships are contemplated.

show abstract

Section: Immunopathogenesis Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities

Osuchowski

Aletti

Cavaillon

et al. 2020

Shock

View full text Add to dashboard Cite

show abstract

“…The symptoms of COVID-19 patients vary widely, from mild illness to severe diseases including dyspnea, pneumonia, and ultimately death [4][5][6]. SARS-CoV-2 belongs to the β coronaviruses, two of which are potentially fatal, Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV [7][8][9]. No effective vaccines or antiviral drugs are currently available, although they are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2

Shin

Kim

et al. 2020

J. Microbiol. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Materials and Methods Viruses and Cells SARS-CoV-2 (BetaCoV/Korea/KCDC03/2020) was provided by the Korea Centers for Disease Control and Prevention (NCCP43326). Vero cells (CCL-81) were purchased from the American Type Culture Collection (ATCC) and maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (both HyClone, USA). SARS-CoV-2 was expanded in the Vero cells and titers were determined by plaque assay. All experiments were performed in a Biosafety Level 3 (BSL3) facility. Chemical Library and Antibodies The FDA-approved drug library of 1,473 drugs and remdesivir were provided by the Korea Chemical Bank at the Korea Research Institute of Chemical Technology (KRICT). The J2 anti-double-stranded RNA (dsRNA) antibody was purchased from English and Scientific Consulting Kft. (Szirák, Hungary, catalog no.10010200). Alexa Fluor 488-conjugated goat anti-mouse antibody was obtained from Life Technologies (USA, catalog no. A11001). Antiviral Screen One day before infection, Vero cells were seeded in 96-well plates at a density of 1 × 10 4 cells per well. Each compound was added at 20 μM final concentration. Cells were then infected with SARS-CoV-2 at an MOI of 0.5. Three days after infection, the cytopathic effects (CPE) of the virus were determined by microscopic examination. COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread globally and caused serious social and economic problems. The WHO has declared this outbreak a pandemic. Currently, there are no approved vaccines or antiviral drugs that prevent SARS-CoV-2 infection. Drugs already approved for clinical use would be ideal candidates for rapid development as COVID-19 treatments. In this work, we screened 1,473 FDA-approved drugs to identify inhibitors of SARS-CoV-2 infection using cell-based assays. The antiviral activity of each compound was measured based on the immunofluorescent staining of infected cells using anti-dsRNA antibody. Twenty-nine drugs among those tested showed antiviral activity against SARS-CoV-2. We report this new list of inhibitors to quickly provide basic information for consideration in developing potential therapies.

show abstract

“…ORF8b suppresses type I IFN expression, by competing with IKKε for HSP70 interaction, which is required for the activation of IKKε and IRF3 [203]. ORF8b was also found to sequester MDA5-mediated NF-κB activation, RLR-activated IRF3 phosphorylation and CARD-CARD interactions between RIG-I and MAVS [204,205]. MERS-CoV-nsp1 inhibits host gene expression by selectively targeting mRNAs to the nucleus and promoting their degradation [48], while the nsp3-4 polyprotein induces the formation of DMVs, which are associated with viral RNA replication [50].…”

Section: Mers-cov Immune Evasionmentioning

confidence: 98%

An Overview of Current Knowledge of Deadly CoVs and Their Interface with Innate Immunity

Zhang

Gargan

et al. 2021

Viruses

View full text Add to dashboard Cite

Coronaviruses are a large family of zoonotic RNA viruses, whose infection can lead to mild or lethal respiratory tract disease. Severe Acute Respiratory Syndrome-Coronavirus-1 (SARS-CoV-1) first emerged in Guangdong, China in 2002 and spread to 29 countries, infecting 8089 individuals and causing 774 deaths. In 2012, Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) emerged in Saudi Arabia and has spread to 27 countries, with a mortality rate of ~34%. In 2019, SARS-CoV-2 emerged and has spread to 220 countries, infecting over 100,000,000 people and causing more than 2,000,000 deaths to date. These three human coronaviruses cause diseases of varying severity. Most people develop mild, common cold-like symptoms, while some develop acute respiratory distress syndrome (ARDS). The success of all viruses, including coronaviruses, relies on their evolved abilities to evade and modulate the host anti-viral and pro-inflammatory immune responses. However, we still do not fully understand the transmission, phylogeny, epidemiology, and pathogenesis of MERS-CoV and SARS-CoV-1 and -2. Despite the rapid application of a range of therapies for SARS-CoV-2, such as convalescent plasma, remdesivir, hydroxychloroquine and type I interferon, no fully effective treatment has been determined. Remarkably, COVID-19 vaccine research and development have produced several offerings that are now been administered worldwide. Here, we summarise an up-to-date understanding of epidemiology, immunomodulation and ongoing anti-viral and immunosuppressive treatment strategies. Indeed, understanding the interplay between coronaviruses and the anti-viral immune response is crucial to identifying novel targets for therapeutic intervention, which may even prove invaluable for the control of future emerging coronavirus.

show abstract

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism

Cited by 11 publications

References 57 publications

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities

Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2

An Overview of Current Knowledge of Deadly CoVs and Their Interface with Innate Immunity

Contact Info

Product

Resources

About