Biology subjects

Chavez-Fumagalli, M. A.

Publications and source records attributed to Chavez-Fumagalli, M. A..

3 recordsLinked to original sources

bioRxiv2026

Targeting Dengue Virus NS3 Helicase: Biochemical and Computational Evaluation of Catechins from Camellia sinensis as Potential Therapeutic Leads

Dengue virus serotype 2 is a human pathogenic flavivirus encoding non-structural protein 3 (DEN2-NS3), a superfamily-2 viral helicase. DEN2-NS3 contains an N-terminal protease domain and a C-terminal RNA helicase/nucleoside 5'-triphosphatase (NTPase) domain essential for replication. The enzyme utilizes energy from NTP hydrolysis to translocate 3'-to-5' along a duplex RNA substrate. Prompted by the high potency of (--)-epigallocatechin gallate (EGCG) against Zika virus, this study investigated if three catechins, EGCG, (--)-epicatechin gallate (ECG), and (--)-epigallocatechin (EGC), would be potent inhibitors of DEN2-NS3. Enzyme-inhibition assays demonstrated that the catalytic domain, DEN2-NS3(S171-K618), was strongly inhibited by the galloylated catechins (EGCG and ECG), verified by an enzyme-coupled confirmatory assay. Inhibition constants (Ki) and suggestive inhibition modes relative to NTPase activity were Ki = 400 {+/-} 86.6 nM for EGCG (mixed-mode), Ki = 550 {+/-} 250 nM for ECG (uncompetitive), and Ki = 18.3 {+/-} 4.2 {micro}M for EGC (mixed-mode). The coronavirus inhibitor SSYA10-001 inhibited DEN2-NS3 (Ki = 10.2 {+/-} 0.3 {micro}M, mixed-mode). Computational workflows using SiteMap identified a predicted druggable pocket associated with the RNA-binding region, involving residues ASP290, ARG387, ASP409, MET429, HIS487, ASP541, ARG599, and ASP603. Catechins were analyzed through 200-ns molecular dynamics simulations to evaluate binding stability. Computational results revealed that EGCG and ECG maintained high stability, forming highly persistent shared amino acid contacts (>45% occupancy) with ASP603, ARG599, ASP541, and ARG387. Biochemical and computational data support these galloylated catechin leads, suggesting a plausible binding model within an amphipathic pocket. Future structural optimization into stable prodrug derivatives could yield promising antiviral candidates.

biochemistry↗

bioRxiv2024

Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis And In Vitro Efficacy

Leishmaniasis is a neglected tropical disease, caused by distinct Leishmania species, which have significant public health challenges due to treatment limitations such as toxicity, high cost, and drug resistance. This study explores the in vitro potential of Malvidin and Echioidinin as probable antileishmanial agents against Leishmania amazonensis, L. braziliensis, and L. infantum, comparing their efficacy to Amphotericin B (AmpB), a standard drug. Malvidin was more potent than Echioidinin across all parasite stages and species. For L. amazonensis, Malvidins inhibitory concentration (IC50) values were 197.71{+/-}17.20 {micro}M and 258.07{+/-}17 {micro}M (stationary and axenic amastigotes, respectively); whereas Echioidinin revealed IC50 values of 272.99{+/-}29.90 M and 335.96{+/-}19.35 M (stationary and axenic amastigotes, respectively). AmpB showed IC50 values of 0.06{+/-}0.01 {micro}M and 0.10{+/-}0.03 {micro}M, respectively. Malvidin demonstrated lower cytotoxicity activity in mammalian cells with a cytotoxic concentration (CC50) value of 2,920.31{+/-}80.29 {micro}M, while AmpBs showed a value of 1.06{+/-}0.12 {micro}M. Malvidin also exhibited favorable selectivity index (SI) values. Malvidin reduced infection rates by up to 35.75% in L. amazonensis-infected macrophages. In silico analysis uncovered strong binding interactions between Malvidin and enzyme arginase in the three species, with key residues such as HIS139 and PRO258 playing a crucial role. Tissue-specific markers expression analysis highlighted the potential Malvidins modulation of genes involved in oxidative stress and DNA repair, including glyoxalase 1 (GLO1) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). The in vitro and in silico data corroborate the hypothesis that Malvidin is safe and can control the Leishmania parasites as a new natural compound for treatment. To further assess its therapeutic potential, in vivo studies are required to evaluate Malvidins efficacy, safety, and pharmacokinetics in animal models, which will be essential for validating its role as a candidate for leishmaniasis treatment.

bioinformatics↗

bioRxiv2023

PeruNPDB: The Peruvian Natural Products Database for in silico drug screening

Since the number of drugs based on natural products (NPs) represents a large source of novel pharmacological entities, NPs have acquired significance in drug discovery. Peru is considered a megadiverse country with many endemic species of plants, terrestrial, and marine animals, and microorganisms. NPs databases have a major impact on drug discovery development. For this reason, several countries such as Mexico, Brazil, India, and China have initiatives to assemble and maintain NPs databases that are representative of their diversity and ethnopharmacological usage. We describe the assembly, curation, and full chemoinformatic evaluation of the content and coverage in chemical space, as well as the physicochemical attributes and chemical diversity of the initial version of the Peruvian Natural Products Database (PeruNPDB), which contains 280 compounds. Access to PeruNPDB is available for free (https://perunpdb.com.pe/). The PeruNPDBs collection is intended to be used in a variety of tasks, such as virtual screening campaigns against various disease targets or biological endpoints. This emphasizes the significance of biodiversity protection both directly and indirectly on human health.

bioinformatics↗