To hit or not to hit: Large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential

Trigueiro-Louro, João; Correia, Vanessa; Guedes, Rita C.; Brito, Rui M. M.

doi:10.1016/j.virol.2019.04.009

Cited by 17 publications

(21 citation statements)

References 68 publications

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“…This method enables the normalization against redundancy and bias in the MSA (reducing both the effect of bias sampling and penalizing gaps) with the benefit of no loss of evolutionary information [86] . This scoring system has been previously applied with success [88] , [89] , [90] . The conservation degree is presented as a numerical score, within a range of 0 (highly variable site) to 11 (highly conserved site), for each aa in the protein sequence alignment [86] , [87] .…”

Section: Methodsmentioning

confidence: 99%

Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike

Trigueiro-Louro

Correia

Figueiredo-Nunes

et al. 2020

Computational and Structural Biotechnology Journal

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Section: Methodsmentioning

confidence: 99%

Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike

Trigueiro-Louro

Correia

Figueiredo-Nunes

et al. 2020

Computational and Structural Biotechnology Journal

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“…A large number of studies have shown that PockDrug-Server is an optimal predictive model of druggability for apoprotein pockets. hot spot residues in the NS1 protein [40]. In this study, we used PockDrug-Server to predict druggable pockets of HEY2, TNIK and LRP4.…”

Section: Discussionmentioning

confidence: 99%

Prediction of a potential drug target based on protein druggability for thyroid cancer

Yang

Zhang

et al. 2020

Preprint

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Background: Thyroid cancer is a common endocrine malignancy; however, its treatment is still surgical. With the development and application of targeted therapy in cancer treatment, there are great development prospects in researching targeted drugs for thyroid cancer. Methods: Differentially expressed mRNAs between thyroid cancerous tissue and normal thyroid tissues were screened from The Cancer Genome Atlas (TCGA) database. Using weighted gene coexpression network analysis (WGCNA) to build co-expression modules and combined with differentially methylated gene (DMG) analysis. The druggability was analyzed by PockDrug-Server. Due to drug repositioning to seek targeted drugs to treat thyroid cancer we constructed a protein-protein interaction (PPI) network, and screened out a drug target of thyroid cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) were used to analysis the protein enrichment of PPI network. Results: In the present study, the red module was significantly correlated with thyroid cancer. With DMG analysis, we screened out three genes: HEY2 , TNIK and LRP4 . These three genes were hypomethylation in tumors. The druggability based on PockDrug-Server predicted that only TNIK had protein pocket druggability. With PPI model for TNIK, there were ten genes interacted with TNIK. These genes were enriched in the MAPK and Wnt pathways, which are correlated with tumor proliferation, differentiation, and development. Upon searching for drugs against these 10 genes in Drugbank, it was determined that the targeted drug Binimetinib which is MEK1/2 inhibition. Therefore, we hypothesized that Binimetinib can be used as a targeted drug and TNIK can be regard as drug target for thyroid cancer therapy. Conclusion: Our research provides a bioinformatics method for screening drugs target and provides a theoretical basis for targeted therapy for thyroid cancer.

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“…NS1 is a highly conserved [40] and multifunctional protein with approximately 26 kDa molecular weight and 215 to 237 amino acids, resulting from the collinear transcription of the eighth vRNA segment. This viral protein has four different structural regions: two globular domains, a linker region, and a C-terminal disordered "tail".…”

Section: Structure and Functionmentioning

confidence: 99%

“…It was suggested that the build-up of pre-mRNA in the nucleus is a source for cap snatching by the viral polymerase [86]. NS1 has a globally hydrophobic pocket comprising residues Lys110, Ile117, Ile119, Gln121, Val180, Gly183, Gly184 and Trp187, where NS1 binds to two (F2 and F3) of the five zinc fingers of CPSF30 [40]. Outside of this binding pocket, two residues, Phe103 and Met106, maintain the stability of the interaction [87].…”

Section: Function and Protein-protein Interactionsmentioning

confidence: 99%

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The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection

Rosário‐Ferreira

Preto

Melo

et al. 2020

IJMS

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Influenza (flu) is a contagious viral disease, which targets the human respiratory tract and spreads throughout the world each year. Every year, influenza infects around 10% of the world population and between 290,000 and 650,000 people die from it according to the World Health Organization (WHO). Influenza viruses belong to the Orthomyxoviridae family and have a negative sense eight-segment single-stranded RNA genome that encodes 11 different proteins. The only control over influenza seasonal epidemic outbreaks around the world are vaccines, annually updated according to viral strains in circulation, but, because of high rates of mutation and recurrent genetic assortment, new viral strains of influenza are constantly emerging, increasing the likelihood of pandemics. Vaccination effectiveness is limited, calling for new preventive and therapeutic approaches and a better understanding of the virus–host interactions. In particular, grasping the role of influenza non-structural protein 1 (NS1) and related known interactions in the host cell is pivotal to better understand the mechanisms of virus infection and replication, and thus propose more effective antiviral approaches. In this review, we assess the structure of NS1, its dynamics, and multiple functions and interactions, to highlight the central role of this protein in viral biology and its potential use as an effective therapeutic target to tackle seasonal and pandemic influenza.

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To hit or not to hit: Large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential

Cited by 17 publications

References 68 publications

Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike

Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike

Prediction of a potential drug target based on protein druggability for thyroid cancer

The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection

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