Protein Engineering in the Design of Protein-Protein Interactions: SARS-CoV-2 Inhibitors as a Test Case.
Biochemistry
; 60(46): 3429-3435, 2021 11 23.
Article
in English
| MEDLINE | ID: covidwho-1292169
ABSTRACT
The formation of specific protein-protein interactions (PPIs) drive most biological processes. Malfunction of such interactions is the molecular driver of many diseases. Our ability to engineer existing PPIs or create new ones has become a vital research tool. In addition, engineered proteins with new or altered interactions are among the most critical drugs that have been developed in recent years. These include antibodies, cytokines, inhibitors, and others. Here, we provide a perspective on the current status of the methods used to engineer new or altered PPIs. The emergence of the COVID-19 pandemic, which resulted in a worldwide quest to develop specific PPI inhibitors as drugs, provided an up-to-date and state-of-the-art status report on the methodologies for engineering PPIs targeting the interaction of the viral spike protein with its cellular target, ACE2. Multiple, very high affinity binders were generated within a few months using in vitro evolution by itself, or in combination with computational design. The different experimental and computational methods used to block this interaction provide a road map for the future of PPI engineering.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Engineering
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Type of study:
Observational study
Limits:
Humans
Language:
English
Journal:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Acs.biochem.1c00356
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