The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway

Li, Jin Yan; Liao, Ce Heng; Wang, Qiong; Tan, Yong; Luo, Rui; Qiu, Ye; Ge, Xin

doi:10.1016/j.virusres.2020.198074

Cited by 430 publications

(480 citation statements)

References 13 publications

(14 reference statements)

Supporting

Mentioning

455

Contrasting

Unclassified

Order By: Relevance

“…In ORF3a, many low significant mutations are observed in the ion channel (Figure 4). Yet another notable point is a high mutability in the SR stretch of nucleoprotein, which along with the frequent ORF8 mutations justify their role in host immune evasion 62,66 (Figure 4). Several phylogenetic analyses have been carried out to understand the evolution of SARS-COV-2 16,[69][70][71][72] .…”

Section: Discussionmentioning

confidence: 99%

“…S24L, A51V, V62L, A65S, S67F, L84S, F120L and a deletion in ORF8 are found to be common to both the phases. The protein encoded by ORF8 has 121 amino acids and presumed to be responsible for host immune evasion 61,62 . While L84S occurs at a high significance (14% in phase 1 and 8% in phase 2), S24L (2% in phase 2) and V62L (1% in phase 2) occur at a moderate significance (Figure 2, 3).…”

Section: L84s Is a High Significant Mutation In Orf8mentioning

confidence: 99%

See 1 more Smart Citation

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Patro

Sathyaseelan

Uttamrao

et al. 2020

Preprint

View full text Add to dashboard Cite

To accelerate the drug and vaccine development against the severe acute respiratory syndrome virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F-NSP6, P323L-NSP12, D614G-spike, Q57H-ORF3a, G251V-ORF3a, L84S-ORF8, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring mutations and P323L-NSP12 and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85-NSP1 deletion, D268-NSP2 deletion, 112 amino acids deletion in ORF8, a phenylalanine insertion amidst F34-F36 (NSP6) and several co-existing substitution/deletion (I559V & P585S in NSP2, P504L & Y541C in NSP13, G82 & H83 deletions in NSP1 and K141, S142 & F143 deletions in NSP2) mutations. P323L-NSP12, D614G-spike, L37F-NSP6, L84S-ORF8 and the sequences deficient of the high significant mutations has led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations has evolved in the first phase and has already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid protein, ORF3a, ORF8, RNA dependent RNA polymerase and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9, NSP10, NSP8, the envelope protein and NSP4 are highly resistant to mutations and can be exploited for drug/vaccine development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: L84s Is a High Significant Mutation In Orf8mentioning

confidence: 99%

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Patro

Sathyaseelan

Uttamrao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…SASR-CoV2 is a single-stranded RNA virus of positive polarity whose genome is approximately 30 kb in length and encodes for 16 non-structural proteins, four structural and six accessory proteins [7,8]. The SARS-CoV-2 has a total of six accessory proteins including 3a, 6, 7a, 7b, 8 and 10 [9,10]. Among these accessory proteins, ORF8 is a significantly exclusive protein as it is different from another known SARS-CoV and thus associated with high efficiency in pathogenicity transmission [11,12].…”

Section: Introductionmentioning

confidence: 99%

A unique view of SARS-CoV-2 through the lens of ORF8 protein

Hassan¹,

Ghosh

Attrish

et al. 2020

Preprint

View full text Add to dashboard Cite

Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8.

show abstract

“…[15][16][17] Early studies investigating the SARS-CoV-2 N protein show similar results in the suppression of interferon induction. [18][19] INFs are signaling molecules of the innate immune system of the host and have been identified as a crucial component in the early phase of viral disease. In detail, type I and type III interferons serve as the first important step of antiviral defense mechanisms that induce downstream antiviral processes.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Supekar

Shajahan

Gleinich

et al. 2020

Preprint

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19) started at the end of 2019 in Wuhan, China has spread rapidly and became a pandemic. Since there is no therapy available that is proven as fully protective against COVID-19, a vaccine to protect against deadly COVID-19 is urgently needed. Nucleocapsid protein (N protein), is one of the most abundant proteins in coronaviruses and is a potential target for both vaccine development and point of care diagnostics. The variable mass of N protein (45 to 60 kDa), suggests the presence of post-translational modifications (PTMs), and it is critical to clearly define these PTMs to gain the structural understanding necessary for further vaccine research. There have been several reports suggesting that the N protein is phosphorylated but lacks glycosylation. Our comprehensive glycomics and glycoproteomics experiments confirm that the N protein is highly O-glycosylated and also contains significant levels of N-glycosylation. We were able to confirm the presence of O-glycans on seven sites with substantial glycan occupancy, in addition to less abundant O-glycans on four sites. We also detected N-glycans on two out of five potential N-glycosylation sites. Moreover, we were able to confirm one phosphorylation site. Recent studies have indicated that the N protein can serve as an important diagnostic marker for coronavirus disease and a major immunogen by priming protective immune responses. Thus, detailed structural characterization of the N protein may provide useful insights for understanding the roles of glycosylation on viral pathogenesis and also in vaccine design and development.

show abstract

The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway

Cited by 430 publications

References 13 publications

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

A unique view of SARS-CoV-2 through the lens of ORF8 protein

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Contact Info

Product

Resources

About