Among the candidates, a peptide termed GK-7 (GKGDFRI), which was designed by extracting residues ranging from Gl圓53 to Ile359 in the ligand-binding domain of ACE2, exhibited the highest binding affinity (25.1 nM) with the SARS-CoV-2 spike receptor-binding domain (RBD). Herein, we designed and prepared short peptide inhibitors containing 4–6 critical residues of ACE2 that contribute to the interaction with SARS-CoV-2 S1. Angiotensin-converting enzyme-2 (ACE2) is the main receptor of SARS-CoV-2 spike 1 (S1), which mediates viral invasion into host cells. The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global concern and necessitates efficient drug antagonists.
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