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Machine learning assisted classification of staphylococcal biofilm maturity
van Dun, S.C.J.; Knol, R.; Silva-Herdade, Ana S.; Veiga, Ana Salomé; Castanho, Miguel A. R. B.; Nibbering, P.H.; Pijls, B.G.C.W.; van der Does, A.M.An increasing incidence of device-related, biofilm-associated infections has been observed in clinical practice worldwide. In vitro biofilm models are essential to study these burdensome infections and to design and test potential new treatment approaches. However, there is considerable variation in in vitro biofilm models, and a generally accepted systematic description of biofilm maturity - apart from incubat...
A designed cyclic analogue of gomesin has potent activity against Staphylococcu...
Dias, Susana; Pinto, Sandra; Silva-Herdade, Ana S.; Cheneval, Olivier; Craik, David J; Coutinho, Ana; Castanho, Miguel A. R. B.; Henriques, Sónia T.Background: Infections caused by bacterial biofilms are very difficult to treat. The use of currently approved antibiotics even at high dosages often fails, making the treatment of these infections very challenging. Novel antimicrobial agents that use distinct mechanisms of action are urgently needed. Objectives: To explore the use of [G1K,K8R]cGm, a designed cyclic analogue of the antimicrobial peptide gomesin...
Parainfluenza fusion peptide promotes membrane fusion by assembling into oligom...
Valério, Mariana; Mendonça, Diogo A.; Morais, João; Buga, Carolina C.; Cruz, Carlos H.; Castanho, Miguel A. R. B.; Melo, Manuel N.; Soares, Cláudio M.Paramyxoviruses are enveloped viruses harboring a negative-sense RNA genome that must enter the host’s cells to replicate. In the case of the parainfluenza virus, the cell entry process starts with the recognition and attachment to target receptors, followed by proteolytic cleavage of the fusion glycoprotein (F) protein, exposing the fusion peptide (FP) region. The FP is responsible for binding to the target me...
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin co...
Todorovski, Toni; Mendonça, Diogo A.; Fernandes-Siqueira, Lorena O.; Cruz-Oliveira, Christine; Guida, Giuseppina; Valle, Javier; Cavaco, MarcoViral disease outbreaks affect hundreds of millions of people worldwide and remain a serious threat to global health. The current SARS-CoV-2 pandemic and other recent geographically-confined viral outbreaks (severe acute respiratory syndrome (SARS), Ebola, dengue, zika and ever-recurring seasonal influenza), also with devastating tolls at sanitary and socio-economic levels, are sobering reminders in this respec...
Penetrating the blood brain barrier with new peptide porphyrin conjugates havin...
Mendonça, Diogo A.; Bakker, Mariët; Cruz-Oliveira, Christine; Neves, Vera; Angeles Jiménez, Maria; Defaus, Sira; Cavaco, Marco; Veiga, Ana SaloméPassing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (...
Enfuvirtide-protoporphyrin IX dual-loaded liposomes: in vitro evidence of syner...
Figueira, Tiago Nascimento; Domingues, Marco; Illien, Françoise; Cadima Couto, Carla Iris; Todorovski, Toni; Andreu, David; Sagan, SandrineWe have developed a nanocarrier consisting of large unilamellar vesicles (LUVs) for combined delivery of two human immunodeficiency virus type 1 (HIV-1) entry inhibitors, enfuvirtide (ENF) and protoporphyrin IX (PPIX). The intrinsic lipophilicity of ENF and PPIX, a fusion inhibitor and an attachment inhibitor, respectively, leads to their spontaneous incorporation into the lipid bilayer of the LUVs nanocarrier....
Nisin influence on the antimicrobial resistance ability of canine oral enterococci
Cunha, Eva; Janela, Rita; Costa, Margarida; Tavares, Luís; Veiga, Ana Salomé; Oliveira, ManuelaPeriodontal disease (PD) is one of the most common diseases in dogs. Although previous studies have shown the potential of the antimicrobial peptide nisin for PD control, there is no information regarding its influence in the development of antimicrobial resistance or horizontal gene transfer (HGT). Nisin’s mutant prevention concentration (MPC) and selection window (MSW) were determined for a collection of cani...
Effect of pH on the influenza fusion peptide properties unveiled by constant-pH...
Lousa, Diana; Pinto, Antónia R. T.; Campos, Sara R. R.; Baptista, António M.; Veiga, Ana Salomé; Castanho, Miguel A. R. B.; Soares, Cláudio M.The influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the ...
Anti-HIV-1 Activity of pepRF1, a Proteolysis-Resistant CXCR4 Antagonist Derived...
Cadima Couto, Carla Iris; Tauzin, Alexandra; Freire, João Miguel; Figueira, Tiago N.; Silva, Rúben; Pérez-Peinado, Clara; Cunha-Santos, CatarinaThere is an urgent need for the development of new anti-HIV drugs that can complement existing medicines to be used against resistant strains. Here, we report the anti-HIV-1 peptide pepRF1, a human serum-resistant peptide derived from the Dengue virus capsid protein. In vitro, pepRF1 shows a 50% inhibitory concentration of 1.5 nM with a potential therapeutic window higher than 53 000. This peptide is specific f...
Anti-HIV-1 activity of pepRF1, a proteolysis-resistant CXCR4 antagonist derived...
Cadima Couto, Carla Iris; Tauzin, Alexandra; Freire, João Miguel; Figueira, Tiago N.; Silva, Rúben D. M.; Pérez-Peinado, Clara; Cunha-Santos, CatarinaThere is an urgent need for the development of new anti-HIV drugs that can complement existing medicines to be used against resistant strains. Here, we report the anti-HIV-1 peptide pepRF1, a human serum-resistant peptide derived from the Dengue virus capsid protein. In vitro, pepRF1 shows a 50% inhibitory concentration of 1.5 nM with a potential therapeutic window higher than 53 000. This peptide is specific f...