Interdisciplinary researcher in drug discovery, combining artificial intelligence, computational biology, organic synthesis, and cell and tissue biology. Background in Chemistry, Biology, and Morphology (MSc and PhD).
EDUCATION
Chemistry and Biology.
RESEARCH, TEACHING, or OTHER INTERESTS
Histology, Drug Discovery, Molecular Biology, Chemistry
Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil Aline Diogo Marinho, Helyson Lucas Bezerra Braz, João Alison de Moraes Silveira, Danilo Galvão Rocha, Roberta Jeane Bezerra Jorge, et al. Bio Integration, 2025 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China in December 2019, rapidly spread worldwide, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Understanding the structural and functional interactions between the virus and host cells is critical for developing therapeutic strategies. Methods: In this study, we employed in silico docking models to investigate the molecular interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, derived from the Brazilian genome sequence, and seven clinically approved drugs: umifenovir, darunavir, lopinavir, ritonavir, remdesivir, pirfenidone, and oseltamivir. The three-dimensional structure of the Omicron RBD model was generated through homology modeling, and potential active site cavities were predicted within the RBD structure. Results: Among the seven drugs tested, only lopinavir and ritonavir demonstrated significant binding affinities to the RBD. Lopinavir exhibited a binding affinity of −9.8 kcal/mol, forming interactions with residues PHE168, GLY167, SER176, GLN175, GLU166, LEU134, LEU137, TYR171, PHE138, LEU174, and PHE172. Ritonavir showed a binding affinity of −8.9 kcal/mol, interacting with residues ARG148, ASN130, VAL23, SER81, ASN33, PHE29, TYR33, SER31, ASN132, ALA26, ALA30, ALA34, and TYR133.Molecular dynamics simulations confirmed the stability of the complexes formed between lopinavir and ritonavir and the RBD active site. Conclusion: These findings underscore the potential of these protease inhibitors as therapeutic agents targeting the SARS-CoV-2 spike protein.
Toxicologic Profile and Anti-Nociceptive Effect of Two Semi-Synthetic Triterpene Derivatives from Combretum Leprosum in Mice Maria Juliane Passos, Hellíada V. Chaves, Francisco G. Barbosa, Jair Mafezoli, Carlos J. A. Silva-Filho, et al. Bio Integration, 2024 Background and aim: Combretum leprosum Mart. serves as a medicinal plant in traditional Brazilian medicine. The beneficial effects of C. leprosum Mart. are attributed to the triterpene, 3β,6β,16β-trihydroxylup-20(29)-ene (CL-1). Herein we evaluate the toxicity of two semi-synthetic derivatives from CL-1 (CL-P2 and CL-P2A) in vitro and in vivo , and determine the efficacy in zymosan-induced writhing response and the putative mechanism of action. Experimental procedure: Toxicity prediction was assessed using the PROTOX-II and ADMETlab 2.0 prediction tools, and SMILES codes for structure identification. In vitro cytotoxicity of the derivatives was tested using the sulforhodamine B assay in L929 and HaCaT cells at 24, 48, and 72 h. Mice received (oral gavage) CL-P2 or CL-P2A (10 mg/kg/d) for 14 days in in vivo toxicity assays. Blood samples and organs (stomach, liver, and kidneys) were collected for AST/ALT level determination and H&E staining, respectively. The anti-nociceptive effect of CL-P2 and CL-P2A (0.1, 1, or 10 mg/kg) was evaluated in the zymosan-induced writhing response. The peritoneal exudate was collected to determine myeloperoxidase (MPO) and superoxide dismutase (SOD) activity, and nitrite concentration. Results: CL-P-2 and CL-P2A derivatives exhibited low cytotoxicity and did not change body mass, AST/ALT levels, or organ weight. The histopathologic analysis did not reveal significant changes in organs. Both derivatives inhibited the writhing response in a dose-dependent manner. In addition, both derivatives failed to reduce MPO activity. However, CL-P2A increased SOD activity and CL-P2 decreased nitrite/nitrate levels. Conclusion: CL-P2 and CL-P2A were shown to exhibit anti-nociceptive effects without toxicity. Our data suggest that CL-P2 and CL-P2A efficacy is mediated, at least in part, via antioxidant activity by modulating nitrite/nitrate levels and SOD activity, respectively.
A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity Thais Sibioni Berti Bastos, André Guilherme Portela de Paula, Rebeca Bosso dos Santos Luz, Anali M. B. Garnique, Marco A. A. Belo, et al. Scientific Reports, 2023 Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.
