Tau protein aggregation associated with SARS-CoV-2 main protease

PLoS One. 2023 Aug 21;18(8):e0288138. doi: 10.1371/journal.pone.0288138. eCollection 2023.

Abstract

The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes. The present study describes the possible induction of tau aggregation by the SARS-CoV-2 3CL protease (3CLpro) possibly relevant in neuropathology. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Coronavirus 3C Proteases* / metabolism
  • Endopeptidases
  • Humans
  • Peptide Hydrolases
  • Protein Aggregates*
  • SARS-CoV-2
  • tau Proteins* / metabolism

Substances

  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases
  • Endopeptidases
  • Peptide Hydrolases
  • Protein Aggregates
  • tau Proteins

Grants and funding

D.W. is supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project-ID 267205415, SFB 1208. sFIDA was supported by the programs “Biomarkers Across Neurodegenerative Diseases I + II” of The Alzheimer’s Association, Alzheimer’s Research UK and the Weston Brain Institute (11084 and BAND-19-614337). We are also grateful for support from The Michael J. Fox Foundation for Parkinson’s Research (14977, 009889), from the ALS Association and from the Packard Center (19-SI-476). We received further funding from the Deutsche Forschungsgemeinschaft (INST 208/616-1 FUGG, INST 208/794-1 FUGG) and the Helmholtz Association (HVF0079).