| Property | Value |
|---|
|
?:abstract
|
-
We present a near-term treatment strategy to tackle pandemic outbreaks of coronaviruses with no specific drugs/vaccines by combining evolutionary and physical principles to identify conserved viral domains containing druggable Zn-sites that can be targeted by clinically safe Zn-ejecting compounds By applying this strategy to SARS-CoV-2 polyprotein-1ab, we predicted multiple labile Zn-sites in papain-like cysteine protease (PL supro /su), nsp10 transcription factor, and nsp13 helicase These are attractive drug targets because they are highly conserved among coronaviruses and play vital structural/catalytic roles in viral proteins indispensable for viral replication We show that five Zn-ejectors can release Zn su2+ /sufrom PL supro /suand nsp10, and clinically-safe disulfiram and ebselen can covalently bind to the Zn-bound/catalytic cysteines in both proteins Notably, disulfiram and ebselen inhibited PL supro /suprotease activity with IC su50 /suin the mM range We propose combining disulfiram/ebselen with broad-spectrum antivirals/drugs to target different conserved domains acting at various stages of the virus life cycle to synergistically inhibit SARS-CoV-2 replication and reduce the emergence of drug resistance
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:license
|
|
|
?:publication_isRelatedTo_Disease
|
|
|
is
?:relation_isRelatedTo_publication
of
|
|
|
?:source
|
|
|
?:title
|
-
Multi-Targeting of Functional Cysteines in Multiple Conserved SARS-CoV-2 Domains by Clinically Safe Zn-ejectors
|
|
?:type
|
|
|
?:who_covidence_id
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}