Open AccessThe role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors
Author(s) -
Anja Pišlar,
Ana Mitrović,
Jerica Sabotič,
Urša Pečar Fonović,
Milica Perišić Nanut,
Tanja Jakoš,
Emanuela Senjor,
Janko Kos
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009013
Subject(s) - biology , cathepsin , polyproteins , viral replication , cathepsin l , viral envelope , virology , cysteine , coronavirus , viral entry , rna , cathepsin b , microbiology and biotechnology , virus , biochemistry , enzyme , gene , covid-19 , medicine , disease , pathology , infectious disease (medical specialty)
Over the last 2 decades, several coronaviruses (CoVs) have crossed the species barrier into humans, causing highly prevalent and severe respiratory diseases, often with fatal outcomes. CoVs are a large group of enveloped, single-stranded, positive-sense RNA viruses, which encode large replicase polyproteins that are processed by viral peptidases to generate the nonstructural proteins (Nsps) that mediate viral RNA synthesis. Papain-like peptidases (PLPs) and chymotrypsin-like cysteine 3C-like peptidase are essential for coronaviral replication and represent attractive antiviral drug targets. Furthermore, CoVs utilize the activation of their envelope spike glycoproteins by host cell peptidases to gain entry into cells. CoVs have evolved multiple strategies for spike protein activation, including the utilization of lysosomal cysteine cathepsins. In this review, viral and host peptidases involved in CoV cell entry and replication are discussed in depth, with an emphasis on papain-like cysteine cathepsins. Furthermore, important findings on cysteine peptidase inhibitors with regard to virus attenuation are highlighted as well as the potential of such inhibitors for future treatment strategies for CoV-related diseases.