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2.
Emerg Infect Dis ; 28(12): 2575-2577, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36347270

RESUMO

Worldwide, millions of persons have received multiple COVID-19 vaccinations and subsequently recovered from SARS-CoV-2 Omicron breakthrough infections. In 2 small, matched cohorts (n = 12, n = 24) in Denmark, we found Omicron BA.1/BA.2 breakthrough infection after 3-dose BNT162b2 vaccination provided improved Omicron BA.5 neutralization over 3-dose vaccination alone.


Assuntos
COVID-19 , Vacinas Virais , Humanos , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos Antivirais , Anticorpos Neutralizantes
4.
Org Lett ; 24(3): 804-808, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35045257

RESUMO

A chemical investigation of the filamentous fungus Aspergillus californicus led to the isolation of a polyketide-nonribosomal peptide hybrid, calipyridone A (1). A putative biosynthetic gene cluster cpd for production of 1 was next identified by genome mining. The role of the cpd cluster in the production of 1 was confirmed by multiple gene deletion experiments in the host strain as well as by heterologous expression of the hybrid gene cpdA inAspergillus oryzae. Moreover, chemical analyses of the mutant strains allowed the biosynthesis of 1 to be elucidated. The results indicate that the generation of the 2-pyridone moiety of 1 via nucleophilic attack of the iminol nitrogen to the carbonyl carbon is different from the biosynthesis of other fungal 2-pyridone products through P450-catalyzed tetramic acid ring expansions. In addition, two biogenetic intermediates, calipyridones B and C, showed modest inhibition effects on the plaque-forming ability of SARS-CoV-2.


Assuntos
Aspergillus/metabolismo , Piridonas/metabolismo , Aspergillus oryzae/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Deleção de Genes , Humanos , Família Multigênica/genética , Policetídeos/metabolismo , Policetídeos/farmacologia , Piridonas/farmacologia , Pirrolidinonas/metabolismo , Pirrolidinonas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
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