In-Silico Studies for the Inhibition of Proprotein Convertase Furin using Synthetic Compound Databases to see the Effectiveness against SARS-CoV-2 Transmission

By : Gursimran Kaur Uppal , Aparna Patil Kose , Saiprasad Ajgaonkar , Suraj Sen , Nilesh Pal

Page No: 411-420

Abstract
In December 2019, cases of the new coronavirus disease 2019 (COVID-19), caused by a new betacoronavirus (SARS-CoV-2), were first reported in Wuhan, China. These cases were characterized by acute pneumoniaassociated symptoms, such as fever, dry cough, chills, shortness of breath, and muscle pain. On comparing SARS-CoV-2 with SARS-CoV, significant differences were observed in the sequence of the S gene of SARSCoV-2, including three short insertions in the N-terminal domain, changes in four out of five of the crucial residues in the receptor-binding motif, and the presence of an unexpected furin cleavage site at the S1/ S2 boundary of the SARS-CoV-2 spike glycoprotein. This insertion is a novel feature that differentiates SARS-CoV-2 from SARS-CoV and several SARS-related coronaviruses (SARSr-CoVs). The SARS-CoV-2 Spike (S) protein, which is the viral protein responsible for binding the ACE2 receptor on the host cell. Prior to and after attachment, the S needs to be activated by cellular proteases (e.g. furin, TMPRSS2), triggering the virus’ entry into the target cell. Presence of a multibasic site, an amino acid motif recognised by furin protease, and whose cleavage activates the S protein. Hence researchers are exploring furin inhibitors against SARS-CoV-2 infection. In our study we have performed virtual screening of natural and synthetic compounds with furin structure (PDB ID: 5JXH). The docking and ADMET results showed that Nafamostat, DAPI, Propamidine, Hydroxystilbamide compounds showed similar activity as per standard drug Diminizine (anti-parasitic drug). Nafamostat compound has shown highest binding affinity with -9.1 kcal/mol against the furin enzyme target and hence it could be considered as a potential inhibitor drug.

Authors :
Gursimran Kaur Uppal, Aparna Patil Kose
Department of Bioinformatics, Guru Nanak Khalsa College of Arts, Science and Commerce, Nathalal Parekh Marg, Matunga, Mumbai, Maharashtra, India.
Saiprasad Ajgaonkar, Suraj Sen and Nilesh Pal
Post Graduate Students, Department of Bioinformatics, Guru Nanak Khalsa College of Arts, Science andCommerce, Nathalal Parekh Marg, Matunga, Mumbai, Maharashtra, India.
 

DOI: https://doi.org/10.32381/JPSR.2022.38.01.44