Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics

Author(s)

Gomes, Caio P. ^[1] ; Fernandes, Danilo E. ^[2] ; Casimiro, Fernanda ^[1] ; Mata, Gustavo F. ^[2] ; Passos, Michelle T. ^[2] ; Varela, Patricia ^[1] ; Mastroianni-Kirsztajn, Gianna ^[2] ; Pesquero, Joao Bosco ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Ctr Res & Mol Diagnost Genet Dis, Dept Biophys, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo - Brazil

• Document type: Review article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 10, DEC 8 2020.
• Web of Science Citations: 1

Abstract

The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease. (AU)

• FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/05266-5 - Detection and functional characterization of genetic mutations in familial and sporadic focal segmental glomerulosclerosis
• Grantee: Gianna Mastroianni Kirsztajn
• Support Opportunities: Regular Research Grants