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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Biomol+Ther+(Seoul) 2021 ; 29 (3): 282-289 Nephropedia Template TP
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Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit #MMPMID33424013
Kandeel M; Yamamoto M; Tani H; Kobayashi A; Gohda J; Kawaguchi Y; Park BK; Kwon HJ; Inoue JI; Alkattan A
Biomol Ther (Seoul) 2021[May]; 29 (3): 282-289 PMID33424013show ga
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 microM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 microM). Peptide #2 inhibited the SARS-CoV-2 pseudovirus assay at IC50=1.49 microM. 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.