Abstract
The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed potent peptides against SARS-CoV-2 infection by carrying out MM-PBSA calculation based on the binding of 52 antiviral peptides (AVPs) to RBD. Considering the binding free energies of AVPs to RBD, cyanovirin-N (CV-N) showed the strongest RBD binding affinity among 52 AVPs. Upon structural analysis of RBD complex with CV-N, it was observed that 12 of the 13 key residues of RBD binding to ACE2 were hijacked by CV-N. CV-N bound to RBD at a smaller affinity of 14.9 nM than that of ACE2 and inhibited the recruitment of S1 to human alveolar epithelial cells. Further analysis revealed that CV-N suppressed SARS-CoV-2 S pseudovirion infection with a half-maximal inhibitory concentration (IC 50 ) of 18.52 μg/mL. This study demonstrated a drug screening for AVPs against SARS-CoV-2 and discovered a peptide with inspiring antiviral properties, which provided a promising strategy for the COVID-19 therapeutic approach.
Keywords: Antiviral peptides; COVID-19; Cyanovirin-N; Molecular simulation; SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2, antiviral peptides, cyanovirin-N, Molecular simulation, 【초록키워드】 coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, ACE2, coronavirus, Antiviral, SARS-COV-2 infection, spike glycoprotein, Infection, peptide, Drug screening, novel coronavirus disease, severe acute respiratory syndrome Coronavirus, binding free energy, binding affinity, Novel coronavirus, Spread, Receptor-binding domain, RBD, peptides, epithelial cells, recruitment, angiotensin-converting enzyme-2, cyanovirin-N, binding, alveolar epithelial cells, AVP, Molecular simulation, Interaction, Therapeutic approach, Analysis, angiotensin, Structural analysis, host cells, host cell, acute respiratory syndrome, half-maximal inhibitory concentration, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, residue, attachment, domain, human Angiotensin-converting enzyme, antiviral properties, RBD binding, SARS-CoV-2 S, binding free energies, RBD complex, Prevent, caused, inhibit, inhibited, provided, demonstrated, suppressed, 【제목키워드】 SARS-CoV-2, drug, Screening, potent, natural, product, Against,