Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2by Targeting the Spike S2 Subunit
10.4062/biomolther.2020.201
- Author:
Mahmoud KANDEEL
1
;
Mizuki YAMAMOTO
;
Hideki TANI
;
Ayako KOBAYASHI
;
Jin GOHDA
;
Yasushi KAWAGUCHI
;
Byoung Kwon PARK
;
Hyung-Joo KWON
;
Jun-ichiro INOUE
;
Abdallah ALKATTAN
Author Information
1. Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2021;29(3):282-289
- CountryRepublic of Korea
- Language:English
-
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.