tetano
Editor, Senior Moderator
Sci Rep
. 2021 Feb 11;11(1):3640.
doi: 10.1038/s41598-021-83229-6.
Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
Ewelina Weglarz-Tomczak[SUP] 1 [/SUP], Jakub M Tomczak[SUP] 2 [/SUP], Michał Talma[SUP] 3 [/SUP], Małgorzata Burda-Grabowska[SUP] 3 4 [/SUP], Mirosław Giurg[SUP] 4 [/SUP], Stanley Brul[SUP] 5 [/SUP]
Affiliations
Abstract
An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PL[SUP]pro[/SUP]) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host's immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PL[SUP]pro[/SUP]. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PL[SUP]pro[/SUP]CoV2. Furthermore, we identified, for the first time, inhibitors of PL[SUP]pro[/SUP]CoV2 showing potency in the nanomolar range. Moreover, we found a difference between PL[SUP]pro[/SUP] from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.
. 2021 Feb 11;11(1):3640.
doi: 10.1038/s41598-021-83229-6.
Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
Ewelina Weglarz-Tomczak[SUP] 1 [/SUP], Jakub M Tomczak[SUP] 2 [/SUP], Michał Talma[SUP] 3 [/SUP], Małgorzata Burda-Grabowska[SUP] 3 4 [/SUP], Mirosław Giurg[SUP] 4 [/SUP], Stanley Brul[SUP] 5 [/SUP]
Affiliations
- PMID: 33574416
- PMCID: PMC7878891
- DOI: 10.1038/s41598-021-83229-6
Abstract
An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PL[SUP]pro[/SUP]) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host's immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PL[SUP]pro[/SUP]. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PL[SUP]pro[/SUP]CoV2. Furthermore, we identified, for the first time, inhibitors of PL[SUP]pro[/SUP]CoV2 showing potency in the nanomolar range. Moreover, we found a difference between PL[SUP]pro[/SUP] from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.