
Sérgio F. SousaUniversity of Porto | UP · Departamento de Biomedicina
Sérgio F. Sousa
PhD
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200
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Publications (200)
Cyanobacteria strains have the potential to produce bioactive compounds that can be used in therapeutics and bioremediation. Therefore, compiling all information about these compounds to consider their value as bioresources for industrial and research applications is essential. In this study, a searchable, updated, curated, and downloadable databas...
The search and development of new quorum-sensing (QS) inhibitors are ongoing processes for biofilm control. Here, we present a protocol for in silico characterization of natural-based molecules as QS inhibitors. We describe steps for preparing models of protein receptors for virtual screening. We then detail procedures for construction and virtual...
In 1990, the discovery of aptamers revolutionized the field of biotechnology with the
introduction of the SELEX methodology (Systematic Evolution of Ligands by
Exponential Enrichment)1. This innovative approach involves an iterative cycle of
binding, washing, and amplification of a randomized pool of nucleotides targeting a
specific molecule or pro...
The rise of antibiotic-resistant bacterial strains has become a critical health concern. According to the World Health Organization, the market introduction of new antibiotics is alarmingly sparse, underscoring the need for novel therapeutic targets. The LytR-CpsA-Psr (LCP) family of proteins, which facilitate the insertion of cell wall glycopolyme...
Opuntia plants are abundant but still underexplored edible resources of the Algerian region. This work chemically characterizes extracts of different parts of the fruit of the commercial Opuntia ficus-indica (L.) Mill. and the wild Opuntia stricta (Haw.) Haw. growing in Bejaia, and evaluates their anti-inflammatory potential through different cell...
Context
Multiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict t...
Plastizyme: a central Hub for plastic biodegradation research
Aptamers show great promise in the field of biotechnology. Our work focuses on the development of a machine learning model for prediction of aptamer-target binding. Therefore, we aim to equip researchers with a tool to not only deepen their understanding of the intricacies of aptamer-target interaction, but to also accelerate research of the possib...
Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae , we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and is...
Xylanases are key biocatalysts in the degradation of the β‐1,4‐glycosidic linkages in the xylan backbone of hemicellulose. These enzymes are potentially applied in a wide range of bioprocessing industries under harsh conditions. Metagenomics has emerged as powerful tools for the bioprospection and discovery of interesting bioactive molecules from e...
The field of aptamer research has been gaining traction in recent years due to their promising versatility and malleability. New computational approaches will be key to further the development and understanding in aptamer research, while also improving its accessibility. Until now, few are the models that aimed to include the three-dimensionality o...
Aims
Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control.
Methods and results
The activity of montelukast and cefopera...
Evolutionary Insights into Plastic-Degrading Enzymes: A Data-Driven Approach to Bioremediation
Exploring the Evolution of PET-Degrading Enzymes: Insights from Sequence Alignment and Phylogenetic Analysis
Creating a Comprehensive Database of Plastic Degrading Enzymes for Machine Learning Applications
Unifying Information on Plastic Degrading Enzymes Across Different Databases
The field of aptamer research has been gaining traction in the past few years, and recent developments in machine learning display promising applications in biological modeling. Despite the exponential growth in the field, a universal platform to host a standardized compilation of known aptamer information has yet to be developed. Our work attempts...
Correction for ‘Exploiting Locusta migratoria as a source of bioactive peptides with anti-fibrosis properties using an in silico approach’ by Carla S. S. Teixeira et al. , Food Funct. , 2024, 15 , 493–502, https://doi.org/10.1039/D3FO04246D.
Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models. Here, we pinpointed taurours...
Edible insects have been proposed as an environmentally and economically sustainable source of protein, being considered as an alternative food, especially to meat . The migratory locust, Locusta migratoria, is...
The secondary metabolites found in cyanobacteria have been reported in several studies. Considering that these cyanobacteria bioactive compounds have applications
across different scientific fields, including anti-cancer therapeutic approaches and anti-bacterial activity, they can be used for developing new or improved biotechnological
methods in t...
Bacterial biofilms are a source of infectious human diseases and are heavily linked to antibiotic resistance. Pseudomonas aeruginosa is a multidrug-resistant bacterium widely present and implicated in several hospital-acquired infections. Over the last years, the development of new drugs able to inhibit Pseudomonas aeruginosa by interfering with it...
Entomophagy is a sustainable alternative source of proteins for human nutrition. Acheta domesticus is one of the three insect species that complies with the European Union Regulation on novel foods, but to date, there are no reports on their potential bioactive peptides. In this study, an in silico approach was applied to simulate the gastrointesti...
The quorum sensing (QS) system is related to cell-to-cell communication as a function of population density, which regulates several physiological functions including biofilm formation and virulence gene expression. QS inhibitors have emerged as a promising strategy to tackle virulence and biofilm development. Among a wide variety of phytochemicals...
PqsD is an anthraniloyl-CoA anthraniloyltransferase involved in the synthesis of the secondary metabolites essential to the formation of Pseudomonas Quinolone Signal (PQS) inducer molecules. Its main substrate is Anthraniloyl-coenzyme A...
Background
Non-B DNA conformations are molecular structures that do not follow the canonical DNA double helix. Mutagenetic instability in nuclear and mitochondrial DNA (mtDNA) genomes has been associated with simple non-B DNA conformations, as hairpins or more complex structures, as G-quadruplexes. One of these structures is Structure A, a cloverle...
Eugenol, a natural phenolic allyl benzene that has been used as an active lead compound showing significant biological activities, including insecticidal effects on a wide variety of domestic arthropod pests, was used as the main reagent in the present work. Ester eugenol derivatives were synthesized and evaluated for their insecticidal activities...
Liposomal formulations were loaded with a new eugenol derivative with insecticidal activity. Molecular modelling has revealed that this compound can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase. A compound-loaded nanoliposome formulation made of natural constituents (egg lecithin and cholesterol) has shown...
A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against Sf9 (Spodoptera frugiperda) insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at...
Retroviral integration into cell chromatin requires the formation of integrase-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes. To further study this mechanism we developed an alphaLISA approach using the prototype foamy virus (PFV) intasome and human nucleosome. This system allowed us to...
The partitioning of the molecular mechanics (MM) energy in calculations involving biomolecular systems is important to identify the source of major stabilizing interactions, e.g., in ligand–protein interactions, or to identify residues with considerable contributions in hybrid multiscale calculations, i.e., quantum mechanics/molecular mechanics (QM...
The eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate 1, with promising insecticidal capability was encapsulated in liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and of 100% dioleoylphosphatidylglycerol (DOPG). Compound-loaded Egg-PC:Ch liposomes exhibit small hydrodynamic diameters (bel...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to...
SARS-CoV-2 Mpro, also known as the main protease or 3C-like protease, is a key enzyme involved in the replication process of the virus that is causing the COVID-19 pandemic. It is also the most promising antiviral drug target targeting SARS-CoV-2 virus. In this work, the catalytic mechanism of Mpro was studied using the full model of the enzyme and...
The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on man...
Increased levels of cathepsin B (CatB), a cysteine protease, have been associated with different types of tumors, including prostate cancer. Hence, the identification of novel targeting ligands homing CatB may be a promising approach for the development of CatB-targeted therapies. In this work, a methodology called systematic evolution of ligands b...
By understanding the mechanism of a stereoselective deacetylation reaction of an acetyloxybenzofuran intermediate to an unusal isoaurone product, the authors could assign the configuration of its glycolic acid precursor obtained from a highly stereoselective benzilic acid rearrangement. This puzzle was solved using state‐of‐the‐art DFT computationa...
The emergence of multi-drug resistant bacteria in the past decades has become one of the major public health issues of our time. One of the main mechanisms of resistance and persistence of bacteria is their ability to form biofilms. Quorum-sensing (QS) is one of the main mechanisms of biofilm formation. Interfering with the QS cascade constitutes a...
An atomistic description of Pdx2 catalytic mechanism is provided by QM/MM methodologies. Pdx2, the glutaminase subunit of pyridoxal 5’-phosphate (PLP) synthase, is characterized by a Cys-His-Glu catalytic triad used to deaminate glutamine to glutamate. While being absent in humans, Pdx2 is essential for the development and replication of the protoz...
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium responsible for acute and chronic infections in planktonic state or in biofilms. The sessile structures are known to confer physical stability, increase virulence, and work as a protective armor against antimicrobial compounds. P. aeruginosa can control the expression of genes, popu...
The benzilic acid rearrangement (BAR) has been exploited with great effect over the last decades, used as the key step in many cases to afford complex target structures with interesting properties. Although the reaction is inherentely stereoselective in cyclic systems, the results achieved using acylic diketone systems can be less satisfactory. Thi...
The present study evaluates the antimicrobial susceptibility of persister cells of Bacillus cereus and Pseudomonas fluorescens after their regrowth in suspension and as biofilms. Two conventional (benzalkonium chloride—BAC and peracetic acid—PAA) and two emerging biocides (glycolic acid—GA and glyoxal—GO) were selected for this study. Persister cel...
Earth-abundant, cheap and non-toxic zinc-based coordination compounds are drawing research attention as promising candidates for various applications, such as photoluminescent materials and anticancer agents. In this paper we report six...
Fighting cancer is one of the major challenges of the 21st century. Among recently proposed treatments, molecular-targeted therapies are attracting particular attention. The potential targets of such therapies include a group of enzymes that possess the capability to catalyze at least two different reactions, so-called multifunctional enzymes. The...
Optimization of Classification Models for the Identification of
Ligand-Target Inhibition Pairs in Biofilm Formation in P.aeruginosa
Epidermal growth factor receptor tyrosine kinase domain (EGFR-TK) has been one of the prominent targets for therapeutics of several human cancers, in particular non-small cell lung cancer. Although several small chemical compounds targeting EGFR-TK have been FDA-approved for treatment of such a cancer, the discovery of a new class of EGFR-TK inhibi...
The catalytic mechanism of Pdx2 was studied with atomic detail employing the computational ONIOM hybrid QM/MM methodology. Pdx2 employs a Cys‐His‐Glu catalytic triad to deaminate glutamine to glutamate and ammonia – the source of the nitrogen of pyridoxal 5’‐phosphate (PLP). This enzyme is, therefore, a rate‐limiting step in the PLP biosynthetic pa...
Here, we report the optimization of a methodology using docking and virtual screening to identify novel clinical uses for already approved drugs. The molecular targets selected were MvfR and PqsD due to their crucial role in quorum sensing and biofilm formation and development. The FDA-approved subset of the ZINC database was screened after careful...
Specific structural modifications in eugenol molecules can simultaneously improve the biological activity and reduce side effects of the respective analogues. The esterification of eugenol by two different experimental procedures, and subsequently the conversion of one of the esters into the corresponding oxirane, was carried out. All derivatives o...
In order to find alternative pesticides, a series of benzamide derivatives was synthesized. An in silico inverted virtual screening protocol considering the 13 common insecticide protein targets was used to evaluate the potential insecticide activity of these molecules and identify the most likely targets. The results suggest important clues for th...
A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpy...
New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containi...
Plastics are highly durable and widely used materials. Current methodologies of plastic degradation, elimination, and recycling are flawed. In recent years, biodegradation (the usage of microorganisms for material recycling) has grown as a valid alternative to previously used methods. The evolution of bioengineering techniques and the discovery of...
With tuberculosis still being one of leading causes of death in the world and the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), researchers have been seeking to find further therapeutic strategies or more specific molecular targets. PknB is one of the 11 Ser/Thr protein kinases of Mtb and is responsible for phosphorylatio...
A non-negligible proportion of human pathogenic variants are known to be present as wild type in at least some non-human mammalian species. The standard explanation for this finding is that molecular mechanisms of compensatory epistasis can alleviate the mutations’ otherwise pathogenic effects. Examples of compensated variants have been described i...
The work, entitled “Development of a Classification Model for the Identification of Targets to Known P.aeruginosa Biofilm Formation Inhibitors”, constitutes an example of how machine learning algorithms can be employed to improve the drug design pipeline and fight biofilm infections more efficiently.
Lactoferrin (Lf), a bioactive milk protein, exhibits strong anticancer and antifungal activities. The search for Lf targets and mechanisms of action is of utmost importance to enhance its effective applications. A common feature among Lf-treated cancer and fungal cells is the inhibition of a proton pump called V-ATPase. Lf-driven V-ATPase inhibitio...
Non-B DNA conformations are molecules that do not follow the canonical double helix DNA structure[1]. This type of molecules, which can assume both simple (e.g. hairpins) and complex (e.g. G-quadruplexes) conformations, are highly related with mutagenetic instability in both nuclear and mitochondrial DNA (mtDNA)[2,3]. We have previously detected a...
Biofilms are aggregates of microorganisms anchored to a surface and embedded in a self-produced matrix of extracellular polymeric substances and have been associated with 80% of all bacterial infections in humans. Because bacteria in biofilms are less amenable to antibiotic treatment, biofilms have been associated with developing antibiotic resista...
Visualization can be a motivating way to teach students about molecules. Nowadays, the available experimental data and accurate computational results allow students to build realistic and accurate molecular models. These models include the representation of complex systems such as proteins, membranes, or nanotubes. However, the visualization of the...