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KMID : 0606920210290030282
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Biomolecules & Therapeutics
2021 Volume.29 No. 3 p.282 ~ p.289
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Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit
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Kandeel Mahmoud
Yamamoto Mizuki
Tani Hideki
Kobayashi Ayako
Gohda Jin
Kawaguchi Yasushi
Park Byoung-Kwon
Kwon Hyung-Joo
Inoue Jun-ichiro
Alkattan Abdallah
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Abstract
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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 SARS-CoV-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.
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KEYWORD
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SARS-CoV-2, COVID-19, Fusion inhibitors, Antiviral drugs
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