Leishmaniasis, a neglected tropical disease caused by Leishmania species, presents serious public health challenges due to limited treatment options, toxicity, high costs, and drug resistance. In this study, the in vitro potential of malvidin and echioidinin is examined as antileishmanial agents against L. amazonensis, L. braziliensis, and L. infantum, comparing their effects to amphotericin B (AmpB), a standard drug. Malvidin demonstrated greater potency than echioidinin across all parasite stages and species. Against L. amazonensis, malvidin’s IC₅₀ values were 197.71 ± 17.20 µM (stationary amastigotes) and 258.07 ± 17 µM (axenic amastigotes), compared to echioidinin’s 272.99 ± 29.90 μM and 335.96 ± 19.35 μM. AmpB was more potent, with IC₅₀ values of 0.06 ± 0.01 µM and 0.10 ± 0.03 µM. Malvidin exhibited lower cytotoxicity (CC₅₀: 2920.31 ± 80.29 µM) than AmpB (1.06 ± 0.12 µM) and a favorable selectivity index. It reduced infection rates by 35.75% in L. amazonensis-infected macrophages. The in silico analysis revealed strong binding between malvidin and Leishmania arginase, with the residues HIS139 and PRO258 playing key roles. Gene expression analysis indicated malvidin’s modulation of oxidative stress and DNA repair pathways, involving genes like GLO1 and APEX1. These findings suggest malvidin’s potential as a safe, natural antileishmanial compound, warranting further in vivo studies to confirm its therapeutic efficacy and pharmacokinetics in animal models.

Nowadays, tuberculosis is the second leading cause of death from a monopathogenic transmitted disease, only ahead of COVID-19. The role of exported repetitive protein (Erp) in the virulence of Mycobacterium tuberculosis has been extensively demonstrated. In vitro and in vivo assays have identified that Erp interacts with Rv1417 and Rv2617c proteins, forming putative transient molecular complexes prior to localization to the cell envelope. Although new insights into the interactions and functions of Erp have emerged over the years, knowledge about its structure and protein–protein interactions at the atomistic level has not been sufficiently explored. In this work, we have combined several in silico methodologies to gain new insights into the structural relationship between these proteins. Two system conditions were evaluated by MD simulations: Rv1417 and Rv2617c embedded in a lipid membrane and another with a semi-polar solvent to mimic the electrostatic conditions on the membrane surface. The Erp protein was simulated as an unanchored structure. Stabilized structures were docked, and complexes were evaluated to recognize the main residues involved in protein–protein interactions. Our results show the influence of the medium on the structural conformation of proteins. Globular conformations were favored under high polarity conditions and showed a higher energetic affinity in complex formation. Meanwhile, disordered conformations were favored under semi-polar conditions and an increase in the number of contacts between residues was observed. In addition, the electrostatic potential analysis showed remarkable changes in protein interactions due to the polarity of the medium, demonstrating the relevance of Erp protein in heterodimer formation. On the other hand, contact analysis showed that several C-terminal residues of Erp were involved in the protein interactions, which seems to contradict experimental observations; however, these complexes could be transient forms. The findings presented in this work are intended to open new perspectives in the studies of Erp protein molecular interactions and to improve the knowledge about its function and role in the virulence of Mycobacterium tuberculosis.

Background Although the COVID-19 pandemic has diminished in intensity, the virus continues to circulate globally. The SARS-CoV-2 main protease (Mpro) is a key enzyme in the life cycle of the virus, making it important for the development of treatments against future variants of the virus. In this work, Peruvian natural compounds were evaluated against different mutations of the SARS-CoV-2 Mpro. Methods In silico techniques such as virtual screening, all-atom molecular dynamics simulations, and energy estimation analysis were applied. Results Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems. Conclusions Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.

Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.

Background The coronavirus disease (COVID-19) pandemic continues to be a public health problem worldwide. Several therapeutic targets of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, whereas the main protease (Mpro) is necessary for virus replication. Since SARS- CoV-2 Mpro mutation rates are inherently high, searching for new inhibitors remains challenging. Herein, this work aimed to evaluate 84 natural compounds from Peruvian sources against different mutations on the Mpro target. Methods We applied virtual screening, all-atom molecular dynamics simulations, and binding free energy estimation by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA). Results The virtual screening results helped us identify rutin as the top compound against different Mpro mutations. Likewise, the computational simulations demonstrated the high structural stability of the Mpro-rutin system. Conclusions his research evaluated the antiviral capacity of Peruvian sources against SARS-CoV-2 Mpro and its mutations, which could be important in preventing and treating SARS-CoV-2 infection.

Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.