Biomol Ther (Seoul) . Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit

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Biomol Ther (Seoul)


. 2021 Jan 11.
doi: 10.4062/biomolther.2020.201. Online ahead of print.
Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit


Mahmoud Kandeel ^{1 2} , Mizuki Yamamoto ³ , Hideki Tani ⁴ , Ayako Kobayashi ³ , Jin Gohda ³ , Yasushi Kawaguchi ^{3 5} , Byoung Kwon Park ⁶ , Hyung-Joo Kwon ⁶ , Jun-Ichiro Inoue ⁷ , Abdallah Alkattan ¹



Affiliations

• PMID: 33424013
• DOI: 10.4062/biomolther.2020.201

Free article

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 ?M concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 ?M). Peptide #2 inhibited the SARSCoV-2 pseudovirus assay at IC50=1.49 ?M. 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.

Keywords: Antiviral drugs; COVID-19; Fusion inhibitors; SARS-CoV-2.