Protein degradation: a novel computational approach to design protein degrader probes for main protease of SARS-CoV-2.
J Biomol Struct Dyn
; : 1-13, 2021 Jul 30.
Article
in English
| MEDLINE | ID: covidwho-2280762
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted many lives and led to approvals of drugs and vaccines for emergency use. Even though vaccines have emerged, the high mortality of COVID-19 and its insurgent proliferation throughout the masses commands an innovative therapeutic proposition for the treatment. Targeted protein degradation has been applied to various disease domains and we propose that it could be incredibly beneficial to tackle the current pandemic. In this study, we have attempted to furnish insights on the design of suitable PROTACs for the main protease (Mpro) of SARS-CoV-2, a protein that is considered to be an essential target for viral replication. We have employed protein-protein docking to predict the possible complementarity between a cereblon E3 ligase and Mpro of SARS-CoV-2, and estimate possible linker length. Molecular Dynamic simulation and analysis on generated ternary complexes demonstrated stable interactions that suggested that designed PROTAC has a potential to cause degradation. The superior characteristics rendered by PROTACS led us to propose them as possibly the next-generation antiviral drugs for SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
Topics:
Vaccines
Language:
English
Journal:
J Biomol Struct Dyn
Year:
2021
Document Type:
Article
Affiliation country:
07391102.2021.1953601
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