The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein – ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.
【저자키워드】 Biochemistry, Drug discovery, structural biology, Computational biology and bioinformatics, 【초록키워드】 COVID-19, SARS-CoV-2, Coronavirus disease 2019, ACE2, Vaccine, pandemic, spike, SARS-CoV, Virtual screening, drug, Infectious disease, docking, in silico, virus, viral entry, FDA approved drug, Spread, Protein, humans, Clinical studies, glycoprotein, molecular, inhibitor, Interaction, Simeprevir, host cell, lumacaftor, host cell membrane, high affinity, receptor ACE2, de novo, SMD, recent, Prevent, effective, robust, shown, identify, caused, significantly, approved, overcome, the receptor-binding domain, reduce, initiate, the Spike, 【제목키워드】 inhibitor, SARS-CoV-2 viral,