Int. J. Mol. Sci. 2021, 22(11), 5670

A Computer-Based Methodology to Design Non-Standard Peptides Potentially Able to Prevent HOX-PBX1-Associated Cancer Diseases

In the last decades, HOX proteins have been extensively studied due to their pivotal role in transcriptional events. HOX proteins execute their activity by exploiting a cooperative binding to PBX proteins and DNA. Therefore, an increase or decrease in HOX activity has been associated with both solid and haematological cancer diseases. Thus, inhibiting HOX-PBX interaction represents a potential strategy to prevent these malignancies, as demonstrated by the patented peptide HTL001 that is being studied in clinical trials. In this work, a computational study is described to identify novel potential peptides designed by employing a database of non-natural amino acids. For this purpose, residue scanning of the HOX minimal active sequence was performed to select the mutations to be further processed. According to these results, the peptides were point-mutated and used for Molecular Dynamics (MD) simulations in complex with PBX1 protein and DNA to evaluate complex binding stability. MM-GBSA calculations of the resulting MD trajectories were exploited to guide the selection of the most promising mutations that were exploited to generate twelve combinatorial peptides. Finally, the latter peptides in complex with PBX1 protein and DNA were exploited to run MD simulations and the ΔGbinding average values of the complexes were calculated. Thus, the analysis of the results highlighted eleven combinatorial peptides that will be considered for further assays.

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Frontiers in cellular and infection microbiology 10, 673

miR-1207-5p Can Contribute to Dysregulation of Inflammatory Response in COVID-19 via Targeting SARS-CoV-2 RNA

The present study focuses on the role of human miRNAs in SARS-CoV-2 infection. An extensive analysis of human miRNA binding sites on the viral genome led to the identification of miR-1207-5p as potential regulator of the viral Spike protein. It is known that exogenous RNA can compete for miRNA targets of endogenous mRNAs leading to their overexpression. Our results suggest that SARS-CoV-2 virus can act as an exogenous competing RNA, facilitating the over-expression of its endogenous targets. Transcriptomic analysis of human alveolar and bronchial epithelial cells confirmed that the CSF1 gene, a known target of miR-1207-5p, is over-expressed following SARS-CoV-2 infection. CSF1 enhances macrophage recruitment and activation and its overexpression may contribute to the acute inflammatory response observed in severe COVID-19. In summary, our results indicate that dysregulation of miR-1207-5p-target genes during SARS-CoV-2 infection may contribute to uncontrolled inflammation in most severe COVID-19 cases.

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BMC bioinformatics 21 (8), 1-10

An improvement of ComiR algorith for microRNA target prediction by exploiting coding region sequences of mRNAs

An improvement of ComiR algorithm for microRNA target prediction by exploiting coding region sequences of mRNAs | BMC Bioinformatics | Full Text MicroRNA are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR is a web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR was trained with the information regarding binding sites in …

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