Drug repurposing for COVID-19 has several potential benefits including shorter development time, reduced costs and regulatory support for faster time to market for treatment that can alleviate the current pandemic. The current study used molecular docking, molecular dynamics and protein-protein interaction simulations to predict drugs from the Drug Bank that can bind to the SARS-CoV-2 spike protein interacting surface on the human angiotensin-converting enzyme 2 (hACE2) receptor. The study predicted a number of peptide-based drugs, including Sar9 Met (O2)11-Substance P and BV2, that might bind sufficiently to the hACE2 receptor to modulate the protein-protein interaction required for infection by the SARS-CoV-2 virus. Such drugs could be validated in vitro or in vivo as potential inhibitors of the interaction of SARS-CoV-2 spike protein with the human angiotensin-converting enzyme 2 (hACE2) in the airway. Exploration of the proposed and current pharmacological indications of the peptide drugs predicted as potential inhibitors of the interaction between the spike protein and hACE2 receptor revealed that some of the predicted peptide drugs have been investigated for the treatment of acute respiratory distress syndrome (ARDS), viral infection, inflammation and angioedema, and to stimulate the immune system, and potentiate antiviral agents against influenza virus. Furthermore, these predicted drug hits may be used as a basis to design new peptide or peptidomimetic drugs with better affinity and specificity for the hACE2 receptor that may prevent interaction between SARS-CoV-2 spike protein and hACE2 that is prerequisite to the infection by the SARS-CoV-2 virus.
【초록키워드】 COVID-19, Treatment, Drug repurposing, Inflammation, viral infection, ARDS, pandemic, Infection, peptide, drugs, molecular docking, Influenza virus, drug, immune system, in vitro, Spike protein, hACE2, airway, Regulatory, specificity, SARS-CoV-2 spike protein, receptor, molecular, in vivo, antiviral agent, inhibitor, predict, protein-protein interaction, acute respiratory distress, Interaction, Support, indication, syndrome, human Angiotensin-converting enzyme, hACE2 receptor, exploration, pharmacological, Prevent, predicted, investigated, required, reduced, peptide-based, faster, the spike protein, modulate, potential benefit, stimulate, alleviate, Bank, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 drug, SARS-CoV-2 spike protein, Interaction, predicted, inhibit, peptide-based,