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Why All the Fury over Furin?
Osman, Essam Eldin A; Rehemtulla, Alnawaz; Neamati, Nouri.
  • Osman EEA; Department of Medicinal Chemistry, College of Pharmacy, Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Rehemtulla A; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • Neamati N; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, United States.
J Med Chem ; 65(4): 2747-2784, 2022 02 24.
Article in English | MEDLINE | ID: covidwho-2275124
ABSTRACT
Analysis of the SARS-CoV-2 sequence revealed a multibasic furin cleavage site at the S1/S2 boundary of the spike protein distinguishing this virus from SARS-CoV. Furin, the best-characterized member of the mammalian proprotein convertases, is an ubiquitously expressed single pass type 1 transmembrane protein. Cleavage of SARS-CoV-2 spike protein by furin promotes viral entry into lung cells. While furin knockout is embryonically lethal, its knockout in differentiated somatic cells is not, thus furin provides an exciting therapeutic target for viral pathogens including SARS-CoV-2 and bacterial infections. Several peptide-based and small-molecule inhibitors of furin have been recently reported, and select cocrystal structures have been solved, paving the way for further optimization and selection of clinical candidates. This perspective highlights furin structure, substrates, recent inhibitors, and crystal structures with emphasis on furin's role in SARS-CoV-2 infection, where the current data strongly suggest its inhibition as a promising therapeutic intervention for SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Peptides / Furin / Small Molecule Libraries / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jmedchem.1c00518

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Peptides / Furin / Small Molecule Libraries / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jmedchem.1c00518