Comprehensive analysis of the host-virus interactome of SARS-CoV-2

Chen, Zhe; Wang, Chao; Feng, Xu; Nie, Litong; Tang, Mengfan; Zhang, Huimin; Xiong, Yun; Swisher, Samuel K; Srivastava, Mrinal; Chen, Junjie

doi:10.1101/2020.12.31.424961

Cited by 14 publications

(20 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several of our other GOF enriched hits have been shown to interact with SARS-CoV-2 viral proteins. The DDX28 helicase interacts with the SARS-CoV-2 N protein and was previously reported to be a protective factor in an RNA interference screen for West Nile virus host factors (Chen et al, 2021;Krishnan et al, 2008). CPNE3, a phospholipid-binding protein, has been implicated as an interaction partner with SARS-CoV-1 nsp1 and viral RNA (Cornillez-Ty et al, 2009;Flynn et al, 2020).…”

Section: Analysis Of Host Restriction Factors Against Sars-cov-2mentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

SUMMARYSARS-CoV-2 can cause a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of the host factors mediating viral infection or restriction is critical to elucidate SARS-CoV-2 host-pathogen interactions and the progression of COVID-19. To this end, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These screens uncovered proviral and antiviral host factors across highly interconnected host pathways, including components implicated in clathrin transport, inflammatory signaling, cell cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high-molecular weight glycoproteins, as a prominent viral restriction network. We demonstrate that multiple membrane-anchored mucins are critical inhibitors of SARS-CoV-2 entry and are upregulated in response to viral infection. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and suggests interactions between SARS-CoV-2 and airway mucins of COVID-19 patients as a host defense mechanism.

show abstract

Section: Analysis Of Host Restriction Factors Against Sars-cov-2mentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 1B, EGFP antibody could detect the WT-NSP3 proteins in GRL0617-treated cells. This observation also explains why a previous study failed to detect the expression of NSP3 using a C-terminal tag [22].…”

Section: Expression Of Nsp3 Proteinsmentioning

confidence: 71%

“…In addition, three very recent interaction studies were performed for SARS-CoV-2 NSP3, with two studies using deletion mutants, whereas the third one failed to detect the expression of NSP3 [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses

Shi

Feng

Zhang

2021

Preprint

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non-structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-kB signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.

show abstract

“…As per our hypothesis, SARS-CoV-2 infection leads to lymphoma remission using a similar mechanism as the brentuximab vedotin exhibits; upon entry into the lymphoma cells, the SARS-COV-2 it will use some of its proteins to initiate cell cycle arrest or apoptosis through interacting with cell cycle machinery components. Gordon et al (38) and Chen et al, (55) reported that M protein and Orf3a of SARS-CoV-2 interact with gamma-tubulin complex components GCP2, GCP3, and TUBG1. The binding of GCP2-TUBG1, GCP3-TUBG1, and GCP2-GCP3 is essential for the microtubule nucleation process (40,41).…”

Section: Discussionmentioning

confidence: 99%

“…According to Gordon et al (38), the SARS-CoV-2 M protein interacts with the human gamma-tubulin complex component 2 (TUBGCP2/ GCP2) and gamma-tubulin complex component 3 (TUBGCP3/GCP3). Similarly, Chen et al, reported that SARS-CoV-2 Orf3a potentially interacts with GCP2, GCP3, and even gamma-tubulin (TUBG1) (39). However, in none of the cases, the authors have provided any further details about the binding sites and the effect of these interactions.…”

Section: The Sars-cov-2 M and Orf3a Proteins Interact With The Human Gamma-tubulin Complex Components And May Inhibit Tubulin Nucleationmentioning

confidence: 99%

Potential anti-tumor immune response mechanisms of SARS-CoV-2 in lymphomas: can the devil be converted into a boon?

Barh

Tiwari

Gomes

et al. 2021

Preprint

View full text Add to dashboard Cite

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on computational approach show that (i) SARS-CoV-2 Spike-RBD may bind to extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL, (ii) upon internalization, SARS-CoV-2 membrane (M) protein and Orf3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site, (iii) M protein may also interact with TUBG1 blocking its binding to GCP3, (iv) both M and Orf3a may render the GCP2-GCP3 lateral binding where M possibly interacts with GCP2 at its GCP3 binding site and Orf3a to GCP3 at its GCP2 interacting residues, (v) interactions of M and Orf3a with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell cycle arrest and apoptosis, (vi) Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab like monoclonal antibodies and may induce B-cell apoptosis and remission, (vii) finally, the TRADD interacting PVQLSY motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 Mpro, nsp7, nsp10, and Spike proteins and may regulate the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in proliferative disorders.

show abstract

Comprehensive analysis of the host-virus interactome of SARS-CoV-2

Cited by 14 publications

References 75 publications

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses

Potential anti-tumor immune response mechanisms of SARS-CoV-2 in lymphomas: can the devil be converted into a boon?

Contact Info

Product

Resources

About