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Why All the Fury over Furin?
Essam Eldin A Osman1,2, Alnawaz Rehemtulla3, Nouri Neamati1
1Department of Medicinal Chemistry, College of Pharmacy, Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of Medicinal Chemistry
|August 3, 2021
Summary
Furin cleavage of the SARS-CoV-2 spike protein aids viral entry. Inhibiting furin, a key enzyme, presents a promising therapeutic strategy for treating SARS-CoV-2 infections and other diseases.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- SARS-CoV-2 possesses a unique multibasic furin cleavage site on its spike protein.
- Furin, a mammalian proprotein convertase, plays a role in viral entry into lung cells.
- Furin is an essential enzyme, but its targeted inhibition is viable in differentiated somatic cells.
Purpose of the Study:
- To highlight the structure, substrates, and inhibitors of furin.
- To emphasize furin's critical role in SARS-CoV-2 pathogenesis.
- To present furin inhibition as a potential therapeutic intervention for viral infections.
Main Methods:
- Sequence analysis of SARS-CoV-2 spike protein.
- Review of existing literature on furin structure, function, and inhibitors.
- Analysis of cocrystal structures of furin inhibitors.
Main Results:
- The multibasic furin cleavage site in SARS-CoV-2 spike protein facilitates viral entry.
- Furin is a druggable target, with several inhibitors and cocrystal structures already developed.
- Furin knockout is not lethal in differentiated somatic cells, supporting therapeutic targeting.
Conclusions:
- Furin-mediated cleavage is crucial for SARS-CoV-2 infectivity.
- Targeting furin offers a promising therapeutic avenue for SARS-CoV-2 and other infections.
- Further optimization of furin inhibitors is warranted for clinical development.
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