Biomol Ther.
2021 May;29(3):282-289. 10.4062/biomolther.2020.201.
Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit
- Affiliations
-
- 1Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- 2Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
- 3Research Center for Asian Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- 4Department of Virology, Toyama Institute of Health, Toyama 939-0363, Japan
- 5Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- 6Department of Microbiology, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea
- 7Senior Professor Office, The University of Tokyo, Tokyo 108-8639, Japan
- KMID: 2515276
- DOI: http://doi.org/10.4062/biomolther.2020.201
Abstract
- A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARSCoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine and associated factors in Japanese hemodialysis patients
- New-Onset Fulminant Type 1 Diabetes Following SARS-CoV-2 Protein Subunit Vaccine: A Case Report and Literature Review
- SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene
- Comparative genetic analyses of Korean bat coronaviruses with SARS-CoV and the newly emerged SARS-CoV-2
- Comparison of Four T-cell Assays and Two Binding Antibody Assays in SARS-CoV-2 Vaccinees With or Without Omicron Breakthrough Infection
