Repositioning of Furin inhibitors as potential drugs against SARS-CoV-2 through computational approaches

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The recent spread of SARS-CoV-2 has led to serious concerns about newly emerging infectious coronaviruses. Drug repurposing is a practical method for rapid development of antiviral agents. The viral spike protein of SARS-CoV-2 binds to its major receptor ACE2 to promote membrane fusion. Following the entry process, the spike protein is further activated by cellular proteases such as TMPRSS2 and Furin to promote viral entry into human cells. A crucial factor in preventing SARS-CoV-2 from entering target cells using HIV-1 fusion inhibitors is the similarity between the fusion mechanisms of SARS-CoV-2 and HIV-1. In this investigation, the HIV-1 fusion inhibitors CMK, Luteolin, and Naphthofluorescein were selected to understand the molecular mode of interactions and binding energy of Furin with these experimental inhibitors. The binding affinity of the three inhibitors with Furin was verified by molecular docking studies. The docking scores of CMK, Luteolin and Naphthofluorescein are −7.4 kcal/mol, −9.3 kcal/mol, and −10.7 kcal/mol, respectively. Therefore, these compounds were subjected to MD, drug-likeness, ADMET, and MM-PBSA analysis. According to the results of a 200 ns MD simulation, all tested compounds show stability with the complex and can be employed as promising inhibitors targeting SARS-CoV-2 Furin protease. In addition, pharmacokinetic analysis revealed that these compounds possess favorable drug-likeness properties. Thus, this study of Furin inhibitors helps in the evaluation of these compounds for use as novel drugs against SARS-CoV-2.