Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This
highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia.
Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along
an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines
clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an
ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to
SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the
activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a
reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key
regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in
COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results
showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells
(PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces
cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential
approach to immunomodulate COVID-19 patients.
Cell Death Discovery (2022) 8:316 ; https://doi.org/10.1038/s41420-022-01115-0