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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, Helena

Influenza 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...


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, Helena

Vaccination 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, Helena

PB1 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...


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, Helena

Influenza 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...


Antiviral drug profile of seasonal influenza viruses circulating in Portugal fr...

Correia, Vanessa; Andrade, Helena Rebelo de; Santos, Luís A.; Lackenby, Angie; Zambon, Maria

A research project on antiviral drug resistance of influenza viruses circulating in Portugal has been carried out since 2007. Here, the first results obtained regarding the evaluation of susceptibility to amantadine and oseltamivir are presented. Information about antiviral prescription and exposure was available through the National Influenza Surveillance Programme. Amantadine susceptibility was evaluated by p...


Antiviral drug profile of seasonal influenza viruses circulating in Portugal fr...

Correia, Vanessa; Rebelo-de-Andrade, Helena; Santos, Luís A.; Lackanby, Angie; Zambon, Maria

A research project on antiviral drug resistance of influenza viruses circulating in Portugal has been carried out since 2007. Here, the first results obtained regarding the evaluation of susceptibility to amantadine and oseltamivir are presented. Information about antiviral prescription and exposure was available through the National Influenza Surveillance Programme. Amantadine susceptibility was evaluated by p...


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