Pandemic Preparedness on Portuguese Podcast

In a recent episode of the Portuguese podcast Palavrões da Ciência, Diana Lousa, co-coordinator of the EvaMobs project, shared insights into the work on building a platform to enhance preparedness for future viral pandemics.

She explained how computational biology, AI, and molecular biology can be applied to accelerate drug development.

Listen to the episode (in Portuguese) to learn more about how our research is helping us prepare for future pandemics!

João B. Vicente

Auxiliary Investigator

João has a background in protein biochemistry and biophysics, with research dedicated to investigating the molecular mechanisms of proteins related to human disease. He leads the APB lab at ITQB NOVA, which specializes in the production of recombinant proteins and their functional and structural characterization using biophysical methods.

In EvaMobs, the APB lab is responsible for bringing the computationally designed Mobs to life. The lab has been implementing screening approaches based on small-scale Mobs production and purification, followed by analysis of thermal stability and binding affinity. Selected hit Mobs are then produced on a larger scale, their biophysical and functional properties analyzed, and sent to consortium partners for further evaluation in other work packages.

Key Publications

CHEK2 germline variants identified in familial nonmedullary thyroid cancer lead to impaired protein structure and function. Pires C, Marques IJ, Valério M, Saramago A, Santo PE, Santos S, Silva M, Moura MM, Matos J, Pereira T, Cabrera R, Lousa D, Leite V, Bandeiras TM, Vicente JB, Cavaco BM. J Biol Chem. 2024 Mar;300(3):105767. doi: 10.1016/j.jbc.2024.105767

Structural and functional impact of clinically relevant E1α variants causing pyruvate dehydrogenase complex deficiency. Pavlu-Pereira H, Lousa D, Tomé CS, Florindo C, Silva MJ, de Almeida IT, Leandro P, Rivera I, Vicente JB. Biochimie. 2021 Apr;183:78-88. doi: 10.1016/j.biochi.2021.02.007.

Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability. Tomé CS, Lopes RR, Sousa PMF, Amaro MP, Leandro J, Mertens HDT, Leandro P, Vicente JB. Sci Rep. 2019 Sep 20;9(1):13615. doi: 10.1038/s41598-019-49944-x.

Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods. Zuhra K, Sousa PMF, Paulini G, Lemos AR, Kalme Z, Bisenieks I, Bisenieks E, Vigante B, Duburs G, Bandeiras TM, Saso L, Giuffrè A, Vicente JB. Sci Rep. 2019 Jan 24;9(1):684. doi: 10.1038/s41598-018-36994-w.

S-Adenosyl-l-methionine Modulates CO and NO• Binding to the Human H2S-generating Enzyme Cystathionine β-Synthase. Vicente JB, Colaço HG, Sarti P, Leandro P, Giuffrè A. J Biol Chem. 2016 Jan 8;291(2):572-81. doi: 10.1074/jbc.M115.681221. Epub 2015 Nov 18.

Cláudio M. Soares

Project Coordinator EvaMobs and Full Professor

Cláudio M. Soares is Full Professor of Biochemistry at ITQB NOVA and Pro-Rector for the NOVAHealth Platform of NOVA University Lisbon. He is also the PI of the Protein Modelling Laboratory of ITQB NOVA and the Coordinator of the Molecular, Structural and Cellular Microbiology – MOSTMICRO-ITQB Research Unit of ITQB NOVA since 2015. He is co-author of 129 papers and has participated in 37 competitively funded projects since 1996. He is a member of the Directive Board of the Portuguese Biophysical Society and President of the Scientific Council of TAGUSPARK – Parque de Ciência e Tecnologia. He was member of the International Union for Pure and Applied Biophysics (IUPAB) council (2011-2017), and member of the Federation of European Biochemical Societies (FEBS) Advanced Courses Committee (2015-2018). Cláudio M. Soares was Dean of ITQB NOVA from 2013 to 2023 and Vice-Dean during 2005-2008 and 2011-2013.

Key Publications

Valério, M, Borges-Araújo, L, Melo, MN, Lousa, D, Soares^*, CM (2022) “SARS-CoV-2 variants impact RBD conformational dynamics and ACE2 accessibility”, Front. Med. Technol., 4:1009451.

Abreu, B, Cruz, C, Oliveira, ASF, Soares, CM (2020) “ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK₂E importer”, Sci.Rep., 11, 10591

Lousa, D, Pinto, ART, Campos, SRR, Baptista, AM, Veiga, AS, Castanho, MARB, Soares, CM (2020) “Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment”, Sci.Rep., 10, 20082

Barbosa, TM, Baltazar, CSA, Cruz, DR, Lousa, D, Soares, CM (2020) “Studying O2 pathways in [NiFe]- and [NiFeSe]-hydrogenases”, Sci.Rep., 10, 10540

Oliveira, ASF, Campos, SRR, Baptista, AM, Soares, CM (2016) “Coupling between protonation and conformation in cytochrome c oxidase: Insights from Constant-pH MD simulations”, BBA Bioenergetics, 1857, 759-771.

Victor, BL, Lousa, D, Antunes, J, Soares, CM (2015) “Self-assembly molecular dynamics simulations shed light into the interaction of the influenza fusion peptide with a membrane bilayer”, J.Chem. Infor. Model., 55, 795–805

Oliveira, ASF, Damas, JM, Baptista, AM, Soares, CM (2014) “Exploring O2 diffusion in A-type Cytochrome c Oxidases: molecular dynamics simulations uncover two alternative channels towards the binuclear site, PLoS Comp.Biol., 10, e1004010

Damas, JM, Baptista, AM, Soares, CM (2014) “The Pathway for O-2 Diffusion inside CotA Laccase and Possible Implications on the Multicopper Oxidases Family”, J Chem Theor Comp, 10, 3525–3531

Antonio Zandona

Scientific Associate

Antonio Zandona, PhD in Chemistry – Biochemistry and Medicinal Chemistry, is an expert in the enzyme kinetics and cell based research, with specific training in flow cytometry and molecular biology techniques. His fields of interest include influence of oxime reactivators and potential drugs on cell level, mechanisms of toxicity on cell level and activation and/or inhibition of signaling pathways with an aim to determine specific mechanisms of toxicity and dependence of compounds structure and toxicity. In addition to being a collaborator on several national and bilateral projects, he was PI of three projects supported by Croatian Academy of Science and Art. As the recipient of EMBO scientific exchange grants he had opportunities to collaborate with leading experts in his field and gain exposure to cutting-edge techniques. His role in the EvaMobs project will be formation and maintenance of the cell bank and performance of specific assays used as a safety assessment in preclinical evaluation of Mobs.

Key Publications

Zandona, Antonio; Madunić, Josip; Miš, Katarina; Maraković, Nikola; Dubois-Goeffroy, Pierre; Cavaco, Marco; Mišetić, Petra; Padovan, Jasna; Castanho, Miguel; Jean, Ludovic et al. Biological response and cell death signaling pathways modulated by tetrahydroisoquinoline-based aldoximes in human cells. Toxicology, 494 (2023) str. 153588-1536. doi: 10.1016/j.tox.2023.153588

Žunec, S.; Vadlja, D.; Ramić, A.; Zandona, A.; Maraković, N.; Brekalo, I.; Primožič, I.; Katalinić, M. Profiling Novel Quinuclidine-Based Derivatives as Potential Anticholinesterase Drugs: Enzyme Inhibition and Effects on Cell Viability. Int. J. Mol. Sci. 2024, 25, 155. https://doi.org/10.3390/ijms25010155

Zandona, Antonio; Jagić, Karla; Dvoršćak, Marija; Madunić, Josip; Klinčić, Darija; Katalinić, Maja. PBDEs found in house dust impact human lung epithelial cell homeostasis. Toxics, 10 (2022), 97-112 doi:10.3390/toxics10020097.

Zandona, Antonio; Maraković, Nikola; Mišetić, Petra; Madunić, Josip; Miš, Katarina; Padovan, Jasna; Pirkmajer, Sergej; Katalinić, Maja. Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes. Archives of toxicology, 95 (2021), 2737-2754. doi:10.1007/s00204-021-03098-w

Zandona, Antonio; Lihtar, Gabriela; Maraković, Nikola; Miš, Katarina; Bušić, Valentina; Gašo- Sokač, Dajana; Pirkmajer, Segej; Katalinić, Maja. Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases. International journal of molecular sciences, 21 (2020), 21; 8088, 19. doi:10.3390/ijms21218088

Maja Katalinić

Scientific Advisor

Maja Katalinić, PhD, has 20 years of experience in the field of drug discovery research and excellent insight into its high demands. She possesses invaluable experience in enzyme kinetics and enzyme biochemistry in general, as well as in evaluating drugs’ effects on the cell level in the early phase of studies. She has passed several trainings in molecular biology as well as training for lab management/leadership. She was a leader and collaborator on national and international projects involving research on antidotes development for the treatment of organophosphorus compounds poisoning, while in 2017 she establish her research group focusing on the molecular mechanisms underlying the toxicity of antidotes and potential drugs. As a leading researcher of IMI team, Dr Katalinić will be responsible for the overall implementation of cell-based in vitro toxicology assays as a safety assessment to evaluate Mobs toxicity.

Key Publications

Žunec, Suzana; Vadlja, Donna; Ramić, Alma; Zandona, Antonio; Maraković, Nikola; Brekalo, Iva; Primožič, Ines; Katalinić, Maja. Profiling Novel Quinuclidine-Based Derivatives as Potential Anticholinesterase Drugs: Enzyme Inhibition and Effects on Cell Viability. International journal of molecular sciences, 25 (2024), 1; 155, 19. doi: doi.org/10.3390/ijms25010155

Miš, Katarina ; Lulić, Ana-Marija ; Marš, Tomaž ; Pirkmajer, Sergej ; Katalinić, Maja. Insulin, dibutyryl-cAMP, and glucose modulate expression of patatin-like domain containing protein 7 in cultured human myotubes. Frontiers in endocrinology (Lausanne), 14 (2023), 1139303, 13. doi: 10.3389/fendo.2023.1139303

Zandona, Antonio; Katalinić, Maja; Šinko, Goran; Radman Kastelic, Andreja; Primožič, Ines; Kovarik, Zrinka. Targeting organophosphorus compounds poisoning by novel quinuclidine-3 oximes: development of butyrylcholinesterase-based bioscavengers. Archives of Toxicology (2020) 94(9): 3157-3171.

Marta Alenquer

Staff Scientist

Marta Alenquer is a virologist with longstanding expertise in herpesviruses, influenza A virus and, more recently, in SARS-CoV-2. Her scientific career has been dedicated to understanding virus-host interactions at both the cellular and organismal levels, identifying host factors and pathways essential for viral replication, as well as viral proteins and virulence factors that impact viral disease in animal models of infection. Since the COVID-19 pandemic, Marta has also been actively involved in the study of antivirals, including anti-SARS-CoV-2 and anti-influenza A virus biopharmaceuticals. In this project, she is involved in in vitro virus-neutralization studies and in vivo antiviral studies of Mobs.

Key Publications

Goncalves J, Melro M, Alenquer M, Araujo C, Castro-Neves J, Amaral-Silva D, Ferreira F, Ramalho J, Charepe N, Serrano F, Pontinha C, Amorim MJ, Soares H (2023) “Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection” JCI Insight e167140. doi: 10.1172/jci.insight.167140

Etibor TA, Sridharan S, Vale-Costa S, Brás S, Becher I, Mello I, Ferreira F, Alenquer M, Savitski M, Amorim MJ (2023) “Defining basic rules for hardening influenza A virus liquid condensates” eLife 12:e85182. doi: 10.7554/eLife.85182

Alenquer M, Milheiro Silva T, Akpogheneta O, Ferreira F, Vale-Costa S, Medina-Lopes M, Batista F, Garcia AM, Barreto VM, Paulino C, Costa J, Sobral J, Diniz-da-Costa M, Ladeiro S, Corte-Real R, Delgado Alves J, Leite RB, Demengeot J, Rocha Brito MJ, Amorim MJ (2022) “Saliva molecular testing bypassing RNA extraction is suitable for monitoring and diagnosing SARS-CoV-2 infection in children” PLOS One 17(6): : e0268388 . doi: 10.1371/journal.pone.0268388

Gonçalves J, Juliano AM*, Charepe N*, Alenquer M*, Athayde D, Ferreira F, Archer M, Amorim MJ, Serrano F, Soares M (2021) “Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination” Cell Reports Medicine 2(12):100468. doi: 10.1016/j.xcrm.2021.100468 *equal contribution

Alenquer M, Ferreira F, Lousa D, Valério M, Medina-Lopes M, Bergman ML, Gonçalves J, Demengeot J, Leite BL, Lilue J, Ning Z, Penha-Gonçalves C, Soares H, Soares CM, Amorim MA (2021) “Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies” PLoS Pathogens 17(8):e1009772. doi: 10.1371/journal.ppat.1009772

Ho JSY, Angel M, Ma Y, Sloan E, Wang G, Martinez-Romero C, Alenquer M, Roudko V, Chung L, Zheng S, Chang M, Fstkchyan Y, Clohisey S, Dinan AM, Gibbs J, Gifford R, Shen R, Gu Q, Irigoyen N, Campisi L, Huang C, Zhao N, Jones JD, van Knippenberg I, Zhu Z, Moshkina N, Meyer L, Noel J, Peralta Z, Rezelj V, Kaake R, Rosenberg B, Wang B, Wei J, Paessler S, Wise HM, Johnson J, Vannini A, Amorim MJ, Baillie JK, Miraldi ER, Benner C, Brierley I, Digard P, Łuksza M, Firth AE, Krogan N, Greenbaum BD, MacLeod MK, van Bakel H, Garcìa-Sastre A, Yewdell JW, Hutchinson E, Marazzi I (2020) “Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection”. Cell 2181(7):1502-1517.e23. doi: 10.1016/j.cell.2020.05.035

Alenquer M*, Vale-Costa S*, Etibor TA, Ferreira F, Sousa AL, Amorim MJ “Influenza A virus ribonucleoproteins form liquid organelles at endoplasmic reticulum exit sites”. (2019) Nature Communications 10: 1629. doi: 10.1038/s41467-019-09549-4

Suzana Žunec

Senior scientific associate

Suzana žunec, PhD in Chemistry – Biochemistry and Medicinal Chemistry, has profiled herself in the field of toxicology. She is experienced in human and animal tissue based research, analysis of biochemical and molecular mechanisms of toxicity of xenobiotics and natural compounds and enzyme kinetics with 18 years of research work. Also, she is trained in chromatographic techniques and analysis of samples. Her research areas include effects of various inorganic and organic pollutants on human health and the environment, protection against chemical weapons and interactions of conventional drugs and herbal products. Her expertise and rich background in toxicology and biochemistry, will contribute to early toxicological evaluation of Mobs – identification of possible toxicities and likelihood of potential adverse events or undesirable effects to allow deciding when it is reasonably safe to proceed to in vivo studies and clinical investigation.

Key Publications

Matošević, Ana; Opsenica, Dejan; Spasić, Marta; Maraković, Nikola; Zandona, Antonio; Žunec, Suzana; Bartolić, Marija; Kovarik, Zrinka; Bosak, Anita. Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer’s disease. Chemico-Biological Interactions, 382 (2023), 110620, 13 doi:10.1016/j.cbi.2023.110620

Žunec S, Brčić Karačonji I, Čatalinac M, Jurič A, Katić A, Kozina G, Micek V, Neuberg M, Lucić Vrdoljak A. Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer. Arh Hig Rada Toksikol 2023;74:198-206 doi.org/10.2478/aiht-2023-74-3765

Jurič A, Brčić Karačonji I, Žunec S, Katić A, Gašić U, Milojković Opsenica D, Kopjar N. Protective role of strawberry tree (Arbutus unedo L.) honey against cyto/genotoxic effects induced by ultraviolet B radiation in vitro. Journal of apicultural research (2022) DOI: 10.1080/00218839.2022.2047421

Zorbaz T, Malinak D, Hofmanova T, Maraković N, Žunec S, Maček Hrvat N, Andrys R, Psotka M, Zandona A, Svobodova J, Prchal L, Fingler S, Katalinić M, Kovarik Z, Musilek K. Halogen substituents enhance oxime nucleophilicity for reactivation of cholinesterases inhibited by nerve agents, European Journal of Medicinal Chemistry,Volume 238, 2022, 114377 doi.org/10.1016/j.ejmech.2022.114377

Diana Lousa

Co-coordinator of EvaMobs and
Assistant Reseracher

Diana Lousa is currently a Researcher at the Protein Modelling Lab, ITQB NOVA. She obtained her PhD in Biochemistry in 2013. The main goal of her current research focuses on the application of computational biophysics to develop tailor-made biopharmaceuticals against viral pathogens such as influenza, zika, HIV, and SARS-CoV-2. She is the co-coordinator of the projects EvaMobs, funded by Horizon Europe (HORIZON-HLTH-2023-DISEASE-03-04), and BioPlaTTAR, funded by the La Caixa Foundation (HR22-00722). She has co-authored 29 articles in peer-reviewed scientific journals, 2 peer-reviewed book chapters, and 34 oral presentations (20 as presenter) in scientific meetings. She has supervised/co-supervised 3 Postdocs, 8 PhD, and 11 Master students, and is the assistant coordinator of the Master in Computational Biology and Bioinformatics at NOVA University. In EvaMobs, she will co-supervise WP1 (computational design of Mobs) and WP6 (project management).

Key Publications

Valério M., Mendonça D. A., Morais J., Buga C. C., Cruz C. H., Castanho M. A R. B., Melo M. N., Soares C. M., Veiga A. S. and Lousa D. (2022), Parainfluenza Fusion Peptide Promotes Membrane Fusion by Assembling into Oligomeric Porelike Structures, ACS Chemical Biology, 17(7), 1831-1843; doi: 10.1021/acschembio.2c00208

Valério M., Borges-Araújo L., Melo M. N., Lousa D., Soares C. M. (2022) SARS-CoV-2 variants impact RBD conformational dynamics and ACE2 accessibility. Front Med Technol. Pharmaceutical innovation, vol. 4:1009451. doi: 10.3389/fmedt.2022.1009451. PMID: 36277437; PMCID: PMC9581196

Lousa, D., & Soares, C. M. (2021). Molecular mechanisms of the influenza fusion peptide: Insights from experimental and simulation studies. FEBS Open Bio, vol. 11(12): 3253-3261. doi:10.1002/2211-5463.13323 –Joint corresponding author

Lousa D., Pinto A. R. T., Campos S. R. R., Baptista A. M., Veiga A. S., Castanho M. A. R. B., Soares C. M. (2020), Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment, Scientific Reports, vol. 10: 20082; doi: 10.1038/s41598-020-77040-y

Sequeira, A. M., Lousa D., Rocha M. (2022) ProPythia: A Python package for protein classification based on machine and deep learning, Neurocomputing, vol. 484: 172-182; doi: 10.1016/j.neucom.2021.07.102