Repurposing FDA-approved drugs for SARS- CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction

Dear Editor,The ongoing coronavirus disease 2019(COVID-19)global pandemic is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which instigates severe and often fatal symptoms.As of September 4th,2020,more than 26 million cases of COVID-19 and almost 900,000 deaths have been reported to WHO.Based on Kissler and colleagues’modeled projections of future viral transmission scenarios,a resurgence in SARS-CoV-2 could occur over the next five years(Kissler et al.,2020).

Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes

Multifunctional factor progranulin(PGRN)plays an important role in lysosomes,and its mutations and insufficiency are associated with lysosomal storage diseases,including neuronal ceroid lipofuscinosis and Gaucher disease(GD).The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation.Challenged PGRN null mice displayed typical features of GD.In addition,GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients.PGRN directly binds to and functions as a chaperone of the lysosomal enzyme β-glucocerebrosidase(GCaase),whose mutations cause GD.In addition,its C-terminus containing granulin E domain,termed Pcgin(PGRN C-terminus for GCase Interaction),is required for the association between PGRN and GCase.The concept that PGRN acts as a chaperone of lysosomal enzymes was further supported and extended by a recent article showing that PGRN acts as a chaperone molecule of lysosomal enzyme cathepsin D(CSTD),and the association between PGRN and CSTD is also mediated by PGRN’s C-terminal granulin E domain.Collectively,these reports suggest that PGRN may act as a shared chaperone and regulates multiple lysosomal enzymes.

A novel mechanism of EAE resistance highlights the conflicting roles of progranulin-mediated immunosuppression and antigen processing

Progranulin(PGRN)is a secreted growth-factor-like molecule with multiple biological functions;elevated PGRN expression correlates with the activity of various autoimmune diseases,including rheumatoid arthritis(RA),inflammatory bowel disease(IBD),and systemic lupus erythematosus(SLE).1,2,3,4 PGRN deficiency is associated with an enhanced inflammatory response and commonly results in increased susceptibility to the onset and progression of various autoimmune conditions in murine models,including inflammatory arthritis,4 inflammatory bowel diseases,5 and inflammatory skin diseases.6 In contrast,PGRN expression has been shown to aggravate some autoimmune conditions,including lupus nephritis.