Influenza passaging annotations: what they tell us and why we should listen

Published date : 30 Jun 2019

Influenza databases now contain over 100,000 worldwide sequence records for strains influenza A(H3N2) and A(H1N1). Although these data facilitate global research efforts and vaccine development practices, they also represent a stumbling block for researchers because of their confusing and heterogeneous annotation. Unclear passaging annotations are particularly concerning given the recent work highlighting the presence and risk of false adaptation signals introduced by cell passaging of viral isolates.

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Journal Paper
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Virus Evolution, Vol. 5, Issue 1, Jan 2019, doi: 10.1093/ve/vez016
Impact Factor
5.408

A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

Published date : 26 Jun 2019

Dengue viruses cause severe and sudden human epidemics worldwide. The secreted form of the nonstructural protein 1 (sNS1) of dengue virus causes vascular leakage, a hallmark of severe dengue disease. Here, we reverse engineered the T164S mutation of NS1, associated with the severity of dengue epidemics in the Americas, into a dengue virus serotype 2 mildly infectious strain. The T164S mutant virus decreased infectious virus production and increased sNS1 production in mammalian cell lines and human peripheral blood mononuclear cells (PBMCs) without affecting viral RNA replication.

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Journal Paper
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Science Translational Medicine, 26 Jun 2019, Vol. 11, Issue 498, doi: 10.1126/scitranslmed.aat772
Impact Factor
16.796

Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties

Published date : 20 Jun 2019

Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus. Specifically, we first generated a library of ATSP-7041 (Chang et al., 2013) analogs iteratively modified by L-Ala and D-amino acids.

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Journal Paper
journal
Molecules 2019, Vol. 24, Issue 12, 2292; https://doi.org/10.3390/molecules24122292
Impact Factor
3.060

Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides

Published date : 17 Jun 2019

Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53-MDM2 protein-protein interaction (PPI). The peptide developed showed complete and selective covalent binding resulting in potent inhibition of p53-MDM2 PPI.

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Journal Paper
journal
Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53–MDM2 protein–protein interaction (PPI). The peptide developed showed complete and selective covalent binding resulting in potent inhibition of p53–MDM2 PPI.
Impact Factor
6.29

Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin

Published date : 10 Jun 2019

In this study, we report antifungal activity of auroramycin against Candida albicans, Candida tropicalis, and Cryptococcus neoformans. Auroramycin, a potent antimicrobial doubly glycosylated 24-membered polyene macrolactam, was previously isolated and characterized, following CRISPR-Cas9 mediated activation of a silent polyketide synthase biosynthetic gene cluster in Streptomyces rosesporous NRRL 15998. Chemogenomic profiling of auroramycin in yeast has linked its antifungal bioactivity to vacuolar transport and membrane organization.

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Journal Paper
journal
PLOS ONE, 10 June 2019, doi: 10.1371/journal.pone.0218189
Impact Factor
2.766

Identification and in vivo Efficacy Assessment of Approved Orally Bioavailable Human Host Protein-Targeting Drugs With Broad Anti-influenza A Activity

Published date : 05 Jun 2019

The high genetic variability of influenza A viruses poses a continual challenge to seasonal and pandemic vaccine development, leaving antiviral drugs as the first line of defense against antigenically different strains or new subtypes. As resistance against drugs targeting viral proteins emerges rapidly, we assessed the antiviral activity of already approved drugs that target cellular proteins involved in the viral life cycle and were orally bioavailable. Out of 15 candidate compounds, four were able to inhibit infection by 10- to 100-fold without causing toxicity, in vitro.

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Journal Paper
journal
Frontiers in Immunology, 5 June 2019, Vol. 10, Article 1097, doi: 10.3389/fimmu.2019.01097
Impact Factor
6.4

Hypocrisy Around Medical Patient Data: Issues of Access for Biomedical Research, Data Quality, Usefulness for the Purpose and Omics Data as Game Changer

Published date : 01 Jun 2019

Whether due to simplicity or hypocrisy, the question of access to patient data for biomedical research is widely seen in the public discourse only from the angle of patient privacy. At the same time, the desire to live and to live without disability is of much higher value to the patients. This goal can only be achieved by extracting research insight from patient data in addition to working on model organisms, something that is well understood by many patients.

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Journal Paper
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Asian Bioethics Review, Jun 2019, Vol. 11, Issue 2, pg 189-207, doi: 10.1007/s41649-019-00085-3

The APD Skin Monitoring App for wound monitoring: Image processing, area plot, and colour histogram

Published date : 30 May 2019

Being often irregular in shape, accurate measurements of wounds are often challenging. Tracing or length measurement by the longest dimension are often inaccurate and time-consuming to carry out. Yet, proper wound area monitoring is essential for wound care. Instead of multiple clinical visits, which also increase the burden on health care systems and the associated expenses, patients can take the responsibility for their own wound progress.

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Journal Paper
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Scientific Phone Apps and Mobile Devices (2019) 5:3, doi: 10.30943/2019/2805019

Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

Published date : 28 May 2019

An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer.

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Journal Paper
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Cancers 2019, Vol. 11, Issue 6, 37, doi: 10.3390/cancers11060737
Impact Factor
5.326

Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723

Published date : 23 May 2019

BACKGROUND:
Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis.

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Journal Paper
journal
BMC Genomics 2019, 20:374, doi: 10.1186/s12864-019-5762-6
Impact Factor
3.730