Journal
BIOMOLECULES & THERAPEUTICS
Volume 29, Issue 3, Pages 282-289Publisher
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2020.201
Keywords
SARS-CoV-2; COVID-19; Fusion inhibitors; Antiviral drugs
Funding
- Administration of International Cooperation and Knowledge Exchange (ICKEA), King Faisal University [IC-01-20]
- Japanese Society for the Promotion of Science [16H06575, 20K07610]
- Program of Japan Initiative for Global Research Network on Infectious Diseases (JGRID) from AMED [JP20wm0125002]
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The study aimed to develop new fusion inhibitors against SARS-CoV-2, designing 12 peptides with peptide #2 demonstrating potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 μM concentration. This shows promise in the development of new prophylactic and therapeutic agents against SARS-CoV-2.
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 mu M concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 mu M). Peptide #2 inhibited the SARS-CoV-2 pseudovirus assay at IC50=1.49 mu 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.
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