Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies

Paolo Fagone; Rosella Ciurleo; Salvo Danilo Lombardo; Carmelo Iacobello; Concetta Ilenia Palermo; Yehuda Shoenfeld; Klaus Bendtzen; Placido Bramanti; Ferdinando Nicoletti

arXiv · 2005.01042

Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies

Paolo Fagone·Rosella Ciurleo·Salvo Danilo Lombardo·Carmelo Iacobello·Concetta Ilenia Palermo·Yehuda Shoenfeld·Klaus Bendtzen·Placido Bramanti·Ferdinando Nicoletti

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Abstract

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has posed a serious threat to global health. As no specific therapeutics are yet available to control disease evolution, more in-depth understanding of the pathogenic mechanisms induced by SARS-CoV-2 will help to characterize new targets for the management of COVID-19. The present study identified a specific set of biological pathways altered in primary human lung epithelium upon SARS-CoV-2 infection, and a comparison with SARS-CoV from the 2003 pandemic was studied. The transcriptomic profiles were also exploited as possible novel therapeutic targets, and anti-signature perturbation analysis predicted potential drugs to control disease progression. Among them, Mitogen-activated protein kinase kinase (MEK), serine-threonine kinase (AKT), mammalian target of rapamycin (mTOR) and I kappa B Kinase (IKK) inhibitors emerged as candidate drugs. Finally, sex-specific differences that may underlie the higher COVID-19 mortality in men are proposed.

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Paolo Fagone, Rosella Ciurleo, Salvo Danilo Lombardo, Carmelo Iacobello, Concetta Ilenia Palermo, Yehuda Shoenfeld, Klaus Bendtzen, Placido Bramanti, Ferdinando Nicoletti. 2020-05-03. Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies. https://arxiv.org/abs/2005.01042

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