23 documents found, page 1 of 3
How to dissect viral infections and their interplay with the host-proteome by i...
Santos, Hugo M.; Carvalho, Luís B.; Lodeiro, Carlos; Martins, Gonçalo; Gomes, Inês L.; Antunes, Wilson D.T.; Correia, Vanessa; Almeida-Santos, Maria M.The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bi...
Optimization of A(H1N1)pdm09 vaccine seed viruses: The source of PB1 and HA vRN...
Almeida, Filipe; Santos, Luís A.; Trigueiro-Louro, João M.; Rebelo-de-Andrade, HelenaVaccination prevents and reduces the severity of influenza virus infections. Continuous evolution of influenza hemagglutinin (HA) and neuraminidase (NA) supports the virus to evade pre-existing immunity, which demands vaccines to be reformulated every year. Incorporation of polymerase basic protein 1 (PB1) viral RNA (vRNA) of the same origin of HA and NA vRNA has been observed in previous pandemic viruses and o...
Adaptive evolution of PB1 from influenza A(H1N1)pdm09 virus towards an enhanced...
Santos, Luís A.; Almeida, Filipe; Gíria, Marta; Trigueiro-Louro, João; Rebelo-de-Andrade, HelenaPB1 influenza virus retain traces of interspecies transmission and adaptation. Previous phylogenetic analyses highlighted mutations L298I, R386K and I517V in PB1 to have putatively ameliorated the A(H1N1)pdm09 adaptation to the human host. This study aimed to evaluate the reversal of these mutations and infer the role of these residues in the virus overall fitness and adaptation. We generate PB1-mutated viruses...
Exploring new antiviral targets for influenza and COVID-19: Mapping promising h...
Figueiredo-Nunes, Inês; Trigueiro-Louro, João; Rebelo-de-Andrade, HelenaInfluenza and COVID-19 are infectious respiratory diseases that represent a major concern to public health with social and economic impact worldwide, for which the available therapeutic options are not satisfactory. The RdRp has a central role in viral replication and thus represents a major target for the development of antiviral approaches. In this study, we focused on Influenza A virus PB1 polymerase protein...
NS1 protein as a novel anti-influenza target: Map-and-mutate antiviral rational...
Trigueiro-Louro, João; Santos, Luís A.; Almeida, Filipe; Correia, Vanessa; Brito, Rui M.M.; Rebelo-de-Andrade, HelenaInfluenza NS1 is a promising anti-influenza target, considering its conserved and druggable structure, and key function in influenza replication and pathogenesis. Notwithstanding, target identification and validation, strengthened by experimental data, are lacking. Here, we further explored our previously designed structure-based antiviral rationale directed to highly conserved druggable NS1 regions across a br...
Unlocking COVID therapeutic targets: A structure-based rationale against SARS-C...
Trigueiro-Louro, João; Correia, Vanessa; Figueiredo-Nunes, Inês; Gíria, Marta; Rebelo-de-Andrade, HelenaThere are no approved target therapeutics against SARS-CoV-2 or other beta-CoVs. The beta-CoV Spike protein is a promising target considering the critical role in viral infection and pathogenesis and its surface exposed features. We performed a structure-based strategy targeting highly conserved druggable regions resulting from a comprehensive large-scale sequence analysis and structural characterization of Spi...
To hit or not to hit: large-scale sequence analysis and structure characterizat...
Trigueiro-Louro, João M.; Correia, Vanessa; Santos, Luís A.; Guedes, Rita C.; Brito, Rui M.M.; Rebelo-de-Andrade, HelenaInfluenza NS1 protein is among the most promising novel druggable anti-influenza target, based on its structure; multiple interactions; and global function in influenza replication and pathogenesis. Notwithstanding, drug development guidance based on NS1 structural biology is lacking. Here, we design a promising strategy directed to highly conserved druggable regions as a result of an exhaustive large-scale seq...
The 1918-1919 Influenza Pandemic in Portugal: a Regional Analysis of Death Impact
Nunes, Baltazar; Silva, Susana; Rodrigues, Ana; Roquette, Rita; Batista, Inês; Rebelo-de-Andrade, HelenaAlthough the impact of deaths occurring during the 1918-1919 influenza pandemic has been assessed in many archeo-epidemiologic studies, detailed estimates are not available for Portugal. We applied negative binomial models to monthly data on respiratory-related and all-cause deaths at the national and district levels from Portugal for 1916-1922. Influenza-related excess mortality was computed as the difference ...
Molecular footprints of selective pressure in the neuraminidase gene of current...
Correia, Vanessa; Abecasis, Ana B.; Rebelo-de-Andrade, HelenaInfluenza neuraminidase (NA) is under selective pressure (SP) of both host immune system and drug use. Here, we assembled large datasets of NA sequences of worldwide circulating viruses to estimate the global and site-specific SP acting on all current subtypes/lineages of human influenza NA. An overall negative SP of similar magnitude and a prevalence of negatively selected sites were observed for all subtypes/...
Revision of clinical case definitions: influenza-like illness and severe acute ...
Fitzner, Julia; Qasmieh, Saba; Mounts, Anthony Wayne; Alexander, Burmaa; Besselaar, Terry; Briand, Sylvie; Brown, Caroline; Clark, Seth; Dueger, EricaThe formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance ...