tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Mizuki Yamamoto[SUP] 3 [/SUP], Hideki Tani[SUP] 4 [/SUP], Ayako Kobayashi[SUP] 3 [/SUP], Jin Gohda[SUP] 3 [/SUP], Yasushi Kawaguchi[SUP] 3 5 [/SUP], Byoung Kwon Park[SUP] 6 [/SUP], Hyung-Joo Kwon[SUP] 6 [/SUP], Jun-Ichiro Inoue[SUP] 7 [/SUP], Abdallah Alkattan[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 [/SUP], Mizuki Yamamoto[SUP] 3 [/SUP], Hideki Tani[SUP] 4 [/SUP], Ayako Kobayashi[SUP] 3 [/SUP], Jin Gohda[SUP] 3 [/SUP], Yasushi Kawaguchi[SUP] 3 5 [/SUP], Byoung Kwon Park[SUP] 6 [/SUP], Hyung-Joo Kwon[SUP] 6 [/SUP], Jun-Ichiro Inoue[SUP] 7 [/SUP], Abdallah Alkattan[SUP] 1 [/SUP]
Affiliations
- PMID: 33424013
- DOI: 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 ?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.