The FEBS journal
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The quest for the effective treatment against coronavirus disease 2019 pneumonia caused by the severe acute respiratory syndrome (SARS)-coronavirus 2(CoV-2) coronavirus is hampered by the lack of knowledge concerning the basic cell biology of the infection. Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS-CoV-2 infection needs to consider the diversity of endocytic pathways available for SARS-CoV-2 entry in the human lung epithelium. ⋯ Furthermore, 11 clinically approved generic drugs are identified as potential candidates for repurposing as blockers of several potential routes for SARS-CoV-2 endocytosis. More broadly, the paradigm of targeting a fundamental aspect of human cell biology to protect against infection may be advantageous in the context of future pandemic outbreaks.
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Senescent cells accumulate with aging and at etiological sites of multiple diseases, including those accounting for most morbidity, mortality, and health costs. Senescent cells do not replicate, can release factors that cause tissue dysfunction, and yet remain viable. ⋯ As anticipated for agents targeting fundamental aging mechanisms that are 'root cause' contributors to multiple disorders, potential applications of senolytics are protean. We review the discovery of senolytics, strategies for translation into clinical application, and promising early signals from clinical trials.
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Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. ⋯ In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNAMet -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP.
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Here, Editor-in-Chief Seamus Martin introduces a new type of article and discusses recent progress at The FEBS Journal, including a marked improvement in the visibility and 'impact' of the journal.
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Editorial Historical Article
50 years of The FEBS Journal: looking back as well as ahead.
In this last issue of 2017, we're celebrating the 50th anniversary of The FEBS Journal. This Editorial considers how the journal has grown and changed from volume 1, issue 1 and outlines our exciting plans for the future.