Targeting SARS-CoV-2 Proteases and Polymerase for COVID-19 Treatment: State of the Art and Future Opportunities.
J Med Chem
; 65(4): 2716-2746, 2022 02 24.
Article
in English
| MEDLINE | ID: covidwho-927546
ABSTRACT
The newly emerged coronavirus, called SARS-CoV-2, is the causing pathogen of pandemic COVID-19. The identification of drugs to treat COVID-19 and other coronavirus diseases is an urgent global need, thus different strategies targeting either virus or host cell are still under investigation. Direct-acting agents, targeting protease and polymerase functionalities, represent a milestone in antiviral therapy. The 3C-like (or Main) protease (3CLpro) and the nsp12 RNA-dependent RNA-polymerase (RdRp) are the best characterized SARS-CoV-2 targets and show the highest degree of conservation across coronaviruses fostering the identification of broad-spectrum inhibitors. Coronaviruses also possess a papain-like protease, another essential enzyme, still poorly characterized and not equally conserved, limiting the identification of broad-spectrum agents. Herein, we provide an exhaustive comparative analysis of SARS-CoV-2 proteases and RdRp with respect to other coronavirus homologues. Moreover, we highlight the most promising inhibitors of these proteins reported so far, including the possible strategies for their further development.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Protease Inhibitors
/
RNA-Dependent RNA Polymerase
/
Coronavirus 3C Proteases
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Limits:
Humans
Language:
English
Journal:
J Med Chem
Journal subject:
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
Acs.jmedchem.0c01140
Similar
MEDLINE
...
LILACS
LIS