tetano
Editor, Senior Moderator
PLoS Pathog
. 2020 Nov 2;16(11):e1009013.
doi: 10.1371/journal.ppat.1009013. eCollection 2020 Nov.
The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors
Anja Pišlar[SUP] 1 [/SUP], Ana Mitrović[SUP] 2 [/SUP], Jerica Sabotič[SUP] 2 [/SUP], Urša Pečar Fonović[SUP] 1 [/SUP], Milica Perišić Nanut[SUP] 2 [/SUP], Tanja Jakoš[SUP] 1 [/SUP], Emanuela Senjor[SUP] 1 2 [/SUP], Janko Kos[SUP] 1 2 [/SUP]
Affiliations
Abstract
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.
. 2020 Nov 2;16(11):e1009013.
doi: 10.1371/journal.ppat.1009013. eCollection 2020 Nov.
The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors
Anja Pišlar[SUP] 1 [/SUP], Ana Mitrović[SUP] 2 [/SUP], Jerica Sabotič[SUP] 2 [/SUP], Urša Pečar Fonović[SUP] 1 [/SUP], Milica Perišić Nanut[SUP] 2 [/SUP], Tanja Jakoš[SUP] 1 [/SUP], Emanuela Senjor[SUP] 1 2 [/SUP], Janko Kos[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33137165
- DOI: 10.1371/journal.ppat.1009013
Abstract
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.