Polyglutamine Repeats in Viruses

Schein, Catherine H.

doi:10.1007/s12035-018-1269-4

Cited by 11 publications

(9 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Along with other RNA viruses including MERS and SARS-CoVs, Q-rich patches are required dsRNA folding domains near the 5′ end of these genomes as reported for SARS-CoVs [47] and Flavivirus [48]. Additionally, there are some other possibilities in different viruses as like dsRNA intermediate formation, roles in the interferon response and viral interfere with the OAS/RNaseL system as discussed recently [44]. Such longer patches of Q-rich regions are not explained previously in RNA viruses specifically coronaviridae.…”

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 84%

“…We have identified two glutamate-rich patches in N protein of SARS-CoV2 as Q-patch1 (20 Qs) and Q-patch2 (16 Qs). Q-patch1 also contents GKGQQQQGQ, which is conserved in N proteins in 1727 genomes of Bat CoVs and SARS-CoVs [44]. Repeats of Q and Q-rich regions are very well described in eukaryotic and viral genomes, which interfere with autophagy by causing viral proteins aggregation [44].…”

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 99%

“…Q-patch1 also contents GKGQQQQGQ, which is conserved in N proteins in 1727 genomes of Bat CoVs and SARS-CoVs [44]. Repeats of Q and Q-rich regions are very well described in eukaryotic and viral genomes, which interfere with autophagy by causing viral proteins aggregation [44]. There are several examples of Q-rich regions assisting in controlling virus replication like bovine leukemia virus infection [45].…”

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 99%

See 2 more Smart Citations

Characterization of Nucleocapsid (N) Protein from Novel Coronavirus SARS-CoV-2

Kumar¹,

Parveen²,

Kumar³

et al. 2020

Preprint

View full text Add to dashboard Cite

Severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has caused the global pandemic as COVID-19, which is the most notorious global public health crisis in the last 100 years. SARS-CoV-2 is composed of four structural proteins and several non-structured proteins. The multi-facet nucleocapsid (N) protein is the major component of structural proteins of CoVs, However, there are no dedicated genomic, sequences and structural analyses focusing on potential roles of N protein. Hence, there is an urgent requirement of a detailed study on N protein of SARS-CoV-2. Herein, we are presenting a comprehensive study on N protein from SARS-CoV-2. We have identified seven motifs conserved in the three major domains namely N-terminal domain, linker regions and the C-terminal domains. Out of seven motifs, six motifs are conserved across different members of coronaviridae, while motif4 is specific for SARS CoVs with potential amyloidogenic properties. Additionally, we report this protein has large patches of disordered regions flanking with these seven motifs. These motifs are hubs of epitopes with 67 experimentally verified epitopes from related viruses. We report the presence of three nuclear localization signals (NLS1-NLS3 mapped to 36-41, 256-26, and 363-389 residues, respectively) and two nuclear export signals (NES1-NLS2 from 151-161 and 217-230 residues, respectively) in the N protein of SARS-CoV-2. These deciphered two Q-patches as Q-patch1 and Q-patch2, mapped in the regions of 266-306, and 361-418 residues, which potentially help in the aggregation of the viral proteins along with 219LALLLLDR226 patch. Additionally, we have identified 14 antiviral drugs potentially binding to seven motifs of N-proteins using docking-based drug discovery methods.

show abstract

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 84%

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 99%

Section: Utilizing Iedb We Have Generated the Largest Epitome Inventomentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Nucleocapsid (N) Protein from Novel Coronavirus SARS-CoV-2

Kumar¹,

Parveen²,

Kumar³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Most phylogenetic analysis of viral sequences start with multiple sequence alignments. Aligning very diverse sequences, especially those containing multiple repeats or insertions, can be quite difficult (28). D-graph, as a flexible sequence analysis tool for protein sequences, provides a valuable first step to obtain an overview of related viral species without the need for an alignment.…”

Section: Discussionmentioning

confidence: 99%

D-graph clusters flaviviruses and β-coronaviruses according to their hosts, disease type and human cell receptors

Braun¹,

Schein

Braun

2020

Preprint

Self Cite

View full text Add to dashboard Cite

Motivation: There is a need for rapid and easy to use, alignment free methods to cluster large groups of protein sequence data. Commonly used phylogenetic trees based on alignments can be used to visualize only a limited number of protein sequences. DGraph, introduced here, is a dynamic programming application developed to generate 2D-maps based on similarity scores for sequences. The program automatically calculates and graphically displays property distance (PD) scores based on physico-chemical property (PCP) similarities from an unaligned list of FASTA files. Such PD-graphs show the interrelatedness of the sequences, whereby clusters can reveal deeper connectivities. Results: PD-Graphs generated for flavivirus (FV), enterovirus (EV), and coronavirus (CoV) sequences from complete polyproteins or individual proteins are consistent with biological data on vector types, hosts, cellular receptors and disease phenotypes. PD-graphs separate the tick- from the mosquito-borne FV, clusters viruses that infect bats, camels, seabirds and humans separately and the clusters correlate with disease phenotype. The PD method segregates the β-CoV spike proteins of SARS, SARS-CoV-2, and MERS sequences from other human pathogenic CoV, with clustering consistent with cellular receptor usage. The graphs also suggest evolutionary relationships that may be difficult to determine with conventional bootstrapping methods that require postulating an ancestral sequence.

show abstract

“…Inhibitors of autophagy may inhibit the growth of RNA viruses that rely on the associated membranes for replication, such as Picornaviruses and Dengue . However, such inhibitors might favor the lytic growth of herpes and other viruses whose replication is held in check by autophagy …”

Section: Finding New Uses For Approved Drugsmentioning

confidence: 99%

Repurposing approved drugs on the pathway to novel therapies

Schein

2019

Medicinal Research Reviews

Self Cite

View full text Add to dashboard Cite

The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.

show abstract

Polyglutamine Repeats in Viruses

Cited by 11 publications

References 115 publications

Characterization of Nucleocapsid (N) Protein from Novel Coronavirus SARS-CoV-2

Characterization of Nucleocapsid (N) Protein from Novel Coronavirus SARS-CoV-2

D-graph clusters flaviviruses and β-coronaviruses according to their hosts, disease type and human cell receptors

Repurposing approved drugs on the pathway to novel therapies

Contact Info

Product

Resources

About