Chagas Disease: Past, Present, and Future

Freilij, Héctor

doi:10.1007/978-3-030-00054-7_1

Cited by 3 publications

(1 citation statement)

References 74 publications

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“…Much effort has been devoted to designing [14][15][16][17][18] or repurposing [19,20] drugs for SARS-CoV-2 targets, but such pursuits have not yet produced breakthrough success. Such disappointment is not surprising, given the historical challenges of developing antiviral therapeutics [21], but it is imperative to persevere and to innovate. The terrible global toll through a few short years of pandemic, the continuing threat of new coronavirus variants and hitherto undiscovered viral pathogens, and the rhetorical value of devising efficacious antiviral strategies all provide powerful incentives.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

Lushington,

Linde,

Melgarejo

2023

BioTech

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(1) Background: The COVID-19 pandemic left many intriguing mysteries. Retrospective vulnerability trends tie as strongly to odd demographics as to exposure profiles, genetics, health, or prior medical history. This article documents the importance of nasal microbiome profiles in distinguishing infection rate trends among differentially affected subgroups. (2) Hypothesis: From a detailed literature survey, microbiome profiling experiments, bioinformatics, and molecular simulations, we propose that specific commensal bacterial species in the Pseudomonadales genus confer protection against SARS-CoV-2 infections by expressing proteases that may interfere with the proteolytic priming of the Spike protein. (3) Evidence: Various reports have found elevated Moraxella fractions in the nasal microbiomes of subpopulations with higher resistance to COVID-19 (e.g., adolescents, COVID-19-resistant children, people with strong dietary diversity, and omnivorous canines) and less abundant ones in vulnerable subsets (the elderly, people with narrower diets, carnivorous cats and foxes), along with bioinformatic evidence that Moraxella bacteria express proteases with notable homology to human TMPRSS2. Simulations suggest that these proteases may proteolyze the SARS-CoV-2 spike protein in a manner that interferes with TMPRSS2 priming.

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Section: Introductionmentioning

confidence: 99%

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

Lushington,

Linde,

Melgarejo

2023

BioTech

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Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

et al. 2022

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Novel Trypanocidal Thiophen-Chalcone Cruzain Inhibitors: Structure- and Ligand-Based Studies

et al. 2022

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Background: Chagas disease is a neglected tropical disease that affects millions of people worldwide and for which no effective treatment is available. Materials & methods: 17 chalcones were synthesized, for which the inhibition of cruzain and trypanocidal activity were investigated. Results: Chalcone C8 showed the highest cruzain inhibitory (IC50 = 0.536 μM) and trypanocidal activity (IC50 = 0.990 μM). Molecular docking studies showed interactions involving Asp161 and the thiophen group interacting with the S2 subsite. Furthermore, quantitative structure–activity relationship ( q2 = 0.786; r2 = 0.953) and density functional theory studies were carried out, and a correlation between the lowest unoccupied molecular orbital surface and trypanocidal activity was observed. Conclusion: These results demonstrate that these chalcones are worthwhile hits to be further optimized in Chagas disease drug discovery programs.

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Chagas Disease: Past, Present, and Future

Cited by 3 publications

References 74 publications

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

Novel Trypanocidal Thiophen-Chalcone Cruzain Inhibitors: Structure- and Ligand-Based Studies

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