Structural Basis for SARS-CoV-2 Nucleocapsid Protein Recognition by Single-Domain Antibodies

Ye, Qiaozhen; Lu, Shan; Corbett, K.D.

doi:10.3389/fimmu.2021.719037

Cited by 46 publications

(37 citation statements)

References 31 publications

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“…Several recent works also reported that SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced liquid-liquid phase separation (LLPS) for its genome packaging and assembly [19][20][21][22]. The SARS-CoV-2 N protein interacts and sequesters key SG proteins including G3BP which leads to attenuation of SG [23][24][25]. These results demonstrate that virus protein can interact with different SG proteins and partition into liquid phases thus indicating the presence of protein-protein interactions.…”

Section: Introductionmentioning

confidence: 80%

“…For identifying the SARS-CoV-2 targeted SG proteins, we first retrieved a list of 809 human proteins targeted by viral proteins from three different SARS-CoV-2 interactome studies [23][24][25]. A list of known mammalian SG proteins was retrieved from the MSGP database.…”

Section: Interaction Network Of Sars-cov-2 Targeted Sg Proteins In the Brainmentioning

confidence: 99%

“…A list of 809 human target proteins known to interact with SARS-CoV-2 viral proteins was retrieved from three different SARS-CoV-2 interactome studies [23][24][25]. The mammalian stress granules proteome (MSGP) database [67] was used for retrieving the list of SG proteins.…”

Section: Identification Of Sars-cov-2 Interacting Human Sg Proteins From Sars-cov-2-human Interactomementioning

confidence: 99%

“…We here employed a network-based system biological framework approach as described previously [28][29][30][31], to investigate the molecular interplay between SARS-CoV-2 proteins and human host SG proteins. We created a brain-specific protein-protein interaction (PPI) network of 116 human SG genes targeted by SARS-CoV-2 reported from previous SARS-CoV-2 interactome studies [23][24][25]. The disease-gene interaction network revealed five key genes linked with the majority of brain-related disorders.…”

Section: Introductionmentioning

confidence: 99%

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Insights into the SARS-CoV-2-Mediated Alteration in the Stress Granule Protein Regulatory Networks in Humans

et al. 2021

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The rapidly and constantly evolving coronavirus, SARS-CoV-2, imposes a great threat to human health causing severe lung disease and significant mortality. Cytoplasmic stress granules (SGs) exert anti-viral activities due to their involvement in translation inhibition and innate immune signaling. SARS-CoV-2 sequesters important SG nucleator proteins and impairs SG formation, thus evading the host response for efficient viral replication. However, the significance of SGs in COVID-19 infection remains elusive. In this study, we utilize a protein-protein interaction network approach to systematically dissect the crosstalk of human post-translational regulatory networks governed by SG proteins due to SARS-CoV-2 infection. We uncovered that 116 human SG proteins directly interact with SARS-CoV-2 proteins and are involved in 430 different brain disorders including COVID-19. Further, we performed gene set enrichment analysis to identify the drugs against three important key SG proteins (DYNC1H1, DCTN1, and LMNA) and also looked for potential microRNAs (miRNAs) targeting these proteins. We identified bexarotene as a potential drug molecule and miRNAs, hsa-miR-615-3p, hsa-miR-221-3p, and hsa-miR-124-3p as potential candidates for the treatment of COVID-19 and associated manifestations.

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Section: Introductionmentioning

confidence: 80%

Section: Interaction Network Of Sars-cov-2 Targeted Sg Proteins In the Brainmentioning

confidence: 99%

Section: Identification Of Sars-cov-2 Interacting Human Sg Proteins From Sars-cov-2-human Interactomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Insights into the SARS-CoV-2-Mediated Alteration in the Stress Granule Protein Regulatory Networks in Humans

et al. 2021

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“…There is evidence that specific antibodies against infectious diseases can be quantified in saliva ( 18 ). Variants of SARS-CoV-2 might be detectable using this current platform, as some research has found that many variants have not had significant changes to the nucleocapsid protein ( 19 ). Furthermore, our assay is also easily adaptable, as the particle conjugation step can be made specific to any new variant once the appropriate antibody becomes commercially available.…”

Section: Discussionmentioning

confidence: 99%

Sensitive, smartphone-based SARS-CoV-2 detection from clinical saline gargle samples

et al. 2022

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Saliva specimens have drawn interest for diagnosing respiratory viral infections due to their ease of collection and decreased risk to healthcare providers. However, rapid and sensitive immunoassays have not yet been satisfactorily demonstrated for such specimens due to their viscosity and low viral loads. Using paper microfluidic chips and a smartphone-based fluorescence microscope, we developed a highly sensitive, low-cost immunofluorescence particulometric SARS-CoV-2 assay from clinical saline gargle samples. We demonstrated the limit of detection of 10 ag/µL. With easy-to-collect saline gargle samples, our clinical sensitivity, specificity, and accuracy were 100%, 86%, and 93%, respectively, for n = 27 human subjects with n = 13 RT-qPCR positives.

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Coupling Single Domain Antibodies to Catalytic Hairpin Assemblies for Homogeneous Assays

Liu,

Zabetakis,

Shriver‐Lake

et al. 2023

Advanced Sensor Research

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Immunoassays are widely used in various fields, including biomedical research, clinical diagnostics, and environmental monitoring. Single domain antibodies (sdAbs) provide small, tailorable, recognition elements that have been integrated into immunoassays for detecting a myriad of targets. Deoxyribonucleic acid (DNA) circuits are synthetic molecular devices composed of DNA strands that can perform logical or computational operations. They have a range of applications, including biosensing, diagnostics, and drug delivery. Recently, an immunoassay method was reported that used catalytic hairpin assemblies (CHA) with antibodies for homogeneous protein detection. The CHA process uses DNA hairpins that interact in the presence of a catalytic DNA sequence. This paper presents a new strategy to couple the recognition of sdAbs with CHA circuits using genetic fusions of sdAbs with rhizavidin (rz), a dimeric biotin binding protein. A pair of sdAb‐rz constructs is each functionalized with a biotinylated DNA sequence that represents half of the catalyst. When both sdAbs bind to the target protein, a signal is generated through the CHA circuit. The split catalyst approach amplifies signals through a DNA circuit without washing steps. Furthermore, this method distinctively utilizes programmable DNA circuits, which are highly modular and can accommodate new targets without disrupting the assay.

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Structural Basis for SARS-CoV-2 Nucleocapsid Protein Recognition by Single-Domain Antibodies

Cited by 46 publications

References 31 publications

Insights into the SARS-CoV-2-Mediated Alteration in the Stress Granule Protein Regulatory Networks in Humans

Insights into the SARS-CoV-2-Mediated Alteration in the Stress Granule Protein Regulatory Networks in Humans

Sensitive, smartphone-based SARS-CoV-2 detection from clinical saline gargle samples

Coupling Single Domain Antibodies to Catalytic Hairpin Assemblies for Homogeneous Assays

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