Anti-protease molecular drug docking studies: SARS-CoV-2 repurposing drug approach
S Poojasri, S Sribal, AK Ramya, P Annathai
The pandemic outbreak of SARS-Coronavirus-2 (SARS-CoV-2) in Wuhan, China on December 2019 caused a fatal and threatening to approximately 1 million cases in 208 countries. The virus entry was achieved by involving its surface glycoprotein and contribution of host cell’s two important proteins ACE2 receptor proteins and TMPRSS2 protease. The TMPRSS2 protease contributed in proteolytic cleavage and allowed priming into the human lung cells for viral entry. Similarly, we retrieved protein sequences from UniProt KB database and modelled 3-Dimensional structure of TMPRSS2 protease using SwissModel since it was not available in PDB database. The main aim of our study is identify potent repurposing FDA approved protease inhibitor using TMPRSS2 protease as protein target. Drug repurposing identifies already existed therapeutically FDA approved drugs for targeting alternative diseases. Thus drugs that have passed phase-I clinical trails with safety response and proved testing in Phase - II, Phase - III can be targeted for some other disease for repurposing. Rather than using new drug development where molecular docking of using repurposing drug can be a useful and quick solution by observing the minimum binding energy for significant insight in the medical emergency to combat Covid-19 fatal infections. The molecular docking results revealed that protease inhibitors Atazanavir (- 11.21), Darunavir (- 11.02), Lopinavir (- 11.73), Saquinavir (- 11.32), and Simeprevir (- 11.10) showed most lowest minimum binding energy when it bound with TMPRSS2 protease. Also, Protein-Ligand interactive amino acids in hydrogen bond formation and hydrophobic interaction analysis were done. Hence, this study suggested to consider these FDA approved drugs for current SARS-CoV-2 treatment.