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Preprint ARTICLE | doi:10.20944/preprints202007.0252.v1

Immunophenotyping of Circulating Leukocytes Reveal Non-specific Activation of Innate and Adaptive Immune Systems in Multi-System Inflammatory Syndrome of Childhood Temporally Associated with SARS-Cov-2 Infection: Descriptive Cohort Study

Michael J. Carter, Matthew Fish, Aislinn Jennings, Katie J. Doores, Paul Wellman, Jeffrey Seow, Sam Acors, Emma Timms, Julia Kenny, Stuart Neil, Michael H. Malim, Shane M. Tibby, Manu Shankar-Hari

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-Co-V2; Paediatric hyperinflammation; MIS-C; PIMS-TS

Online: 12 July 2020 (12:09:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.0138.v1

Approaching High-Performance TS-1 Zeolites in the Presence of Alkali Metal Ions via Combination of Adjusting pH Value and Modulating Crystal Size

Geng Li, Kairui Fu, Fulin Xu, Tianduo Li, Yunan Wang, Jingui Wang

Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: Zeolites; TS-1; Inorganic alkali; Titanium; Lewis acid; Oxidation

Online: 4 July 2023 (08:13:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202311.0097.v1

Machine Learning and Structure-based Virtual Screening for Selecting Cinnamic Acid Derivatives as Leishmania major DHFR-TS Inhibitors

Maria Camila Muñoz-Vega, Sofía López-Hernández, Adrián Sierra-Chavarro, Marcus Tullius Scotti, Luciana Scotti, Ericsson Coy-Barrera, Chonny Herrera-Acevedo

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Leishmania; Asteraceae; DHFR-TS; Lignans; Flavonoids; Natural products; Machine learning.

Online: 1 November 2023 (12:46:39 CET)

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The critical enzyme Dihydrofolate Reductase-Thymidylate Synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. By consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in-silico predictions were then validated through in-vitro assays to examine the inhibitory capacity of the top-ranked naturally-occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4′-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR, with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

Preprint ARTICLE | doi:10.20944/preprints202009.0435.v1

Pediatric Inflammatory Multisystem Syndrome (PIMS) Did Occur in Poland during Months with Low COVID-19 Prevalence. Preliminary Results of a Nationwide Register.

Magdalena Okarska-Napierała, Kamila Ludwikowska, Leszek Szenborn, Natalia Dudek, Anna Mania, Piotr Buda, Janusz Książyk, Katarzyna Mazur-Malewska, Magdalena Figlerowicz, Maciej Szczukocki, Beata Kucińska, Bożena Werner, Lidia Stopyra, Agnieszka Czech, Elżbieta Berdej-Szczot, Aneta Gawlik, Paulina Opalińska, Artur Mazur, Danuta Januszkiewicz-Lewandowska, Cezary Niszczota, Teresa Jackowska, Jacek Wysocki, Paweł Tracewski, Jacek Kusa, Paulina Potocka, Artur Sulik, Katarzyna Ziora, Helena Krakowczyk, Aleksandra Wodniak, Janusz Zaryczański, Alicja Żakiewicz-Cepak, Elżbieta Jarocka-Cyrta, Agnieszka Koczwara, Anna Prusek-Dudkiewicz, Ewa Zbucka-Jachowska, Sabina Langer-Wójcik, Elżbieta Kołodziej, Ernest Kuchar

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: PIMS; MIS-C; SARS-CoV-2; COVID-19; Kawasaki disease; survey

Online: 18 September 2020 (11:29:49 CEST)

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