15 documents found, page 1 of 2
Addressing the challenge of oligomerization in computational protein design
Silva, Diogo; Moreira, Pedro; Teixeira, Rita I.; Fernandes, Bárbara; Parada, Mariana; Vicente, João B.; Lousa, Diana; Soares, Cláudio M.Computational protein design is a field of research with potential to greatly impact areas such as drug development or enzyme technology, by combining knowledge-based and physics-based methods to design tailor-made proteins. This concept was introduced by David Baker with the development of Rosetta Commons. This is an extensive framework containing tools that enable protein design using physics-based scoring fu...
Artificial intelligence-based design of antibody-like engineered protein scaffolds
Salgueiro, André R. F.; Moreira, Pedro; Soares, Cláudio M.; Vanescchi, Leonardo; Lousa, DianaThroughout humanity history, viral outbreaks caused devastating epidemics, like the recent COVID-19, caused by the SARS-CoV-2 virus originating in China. As of December 13, 2023, over 772 million confirmed COVID-19 cases, with more than 6.9 million deaths, have been reported globally to the World Health Organization. Over time, SARS-CoV-2 has evolved into different strains with varied characteristics, including...
Computationally-designed miniproteins showing neutralization activity against S...
Moreira, Pedro Daniel Martins; Parada, Mariana; Fernandes, Bárbara; Buga, Carolina C.; Teixeira, Rita I.; Oliveira, Christine; Buckley, Stephen MichaelAs the COVID-19 pandemic demonstrated, the need for robust antiviral therapies against SARS-CoV-2 remains substantial. A promising strategy to meet this demand is through the development of proteins tailored for enhanced binding affinity to crucial viral targets, such as epitopes located on their fusion proteins. Among these targets is the Spike proteins receptor binding domain (RBD), which interacts with the h...
Computational design of antiviral biologics targeting Zika virus envelope protein
Pereira, Maria Benedita; Moreira, Pedro Daniel Martins; Teixeira, Rita I.; Soares, Cláudio M.; Lousa, DianaIn the past two decades, the world has struggled with recurrent viral outbreaks, with viruses from diverse families demonstrating pandemic and epidemic potential. One of those viruses is the Zika virus. Despite disease cases having declined globally after 2017, Zika virus transmission persists at low levels in regions like the Americas and a total of 89 countries and territories have reported evidence of Zika v...
Antiviral proteins targeting Influenza A hemagglutinin: design, production and ...
Marques, Madalena C.; Moreira, Pedro; Teixeira, Rita I.; Alenquer, Marta; Amorim, Maria João; Soares, Cláudio M.; Vicente, João B.; Lousa, DianaIn recent years we have felt the devastating impact of viral pandemics, highlighting the need for preparation for future pandemics. Antiviral biologics, including small proteins that bind to and block viral targets, are promising therapeutic options that should be explored to increase pandemic preparedness. One of the viruses with high pandemic potential is influenza, the causative agent of flu. Despite being c...
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...
The importance of lipid conjugation on anti-fusion peptides against Nipah virus
Marques, Marta C.; Lousa, Diana; Silva, Patrícia M.; Faustino, André F.; Soares, Cláudio M.; Santos, Nuno C.Nipah virus (NiV) is a recently emerging zoonotic virus that belongs to the Paramyxoviridae family and the Henipavirus genus. It causes a range of conditions, from asymptomatic infection to acute respiratory illness and fatal encephalitis. The high mortality rate of 40 to 90% ranks these viruses among the deadliest viruses known to infect humans. Currently, there is no antiviral drug available for Nipah virus d...
Molecular determinants of the SARS-CoV-2 fusion peptide activity
Buga, Carolina C.; Valério, Mariana; Balola, Alexandra; Ferreira, Ana S.; Sequeira, Ana Marta Fernandes Tavares; Rocha, Miguel; Vicente, João B.The COVID-19 pandemic, caused by the SARS-CoV-2 virus, emerged in late 2019 and quickly spread worldwide, resulting in over 125 million infections and 2.7 million deaths as of March 2021 accordingly to the World Health Organization. Despite the great advances achieved by the scientific community in providing crucial information about this virus, we are still far from completely understanding it. SARS-CoV-2 is a...
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 ...
Study of the interactions of bovine serum albumin with a molybdenum(II) carbony...
Jeremias, Hélia F.; Lousa, Diana; Hollmann, Axel; Coelho, Ana C.; Baltazar, Carla S.; Seixas, João D.; Marques, Ana R.; Santos, Nuno C.Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complex...