Design of specific inhibitor against SARS-CoV-2 3Clpro based on 59S ligand structure in 7WO3.pdb crystal structure using virtual screening methods
Design of specific inhibitor against SARS-CoV-2 3Clpro based on 59S ligand structure in 7WO3.pdb crystal structure using virtual screening methods
Simin sadat attarzadeh behbahani,1Frouzan absalan,2Mostafa Jamalan,3,*
1. Department of Biochemistry, Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran. 2. Department of Anatomy, Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran. 3. Department of Biochemistry, Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran.
Introduction: After the increase in the cases of SARS-Corona Virus 2019 and the global spread of the COVID-19 disease, the World Health Organization (WHO) announced the outbreak of the new coronavirus as the cause of public health emergency worldwide. Due to the pathogenicity of this virus and the consequences caused by it, the production of effective drugs or vacccines against this viral infection has been intensively considered. Today, one of the most important methods of producing specific drugs against bacterial or viral agents is the use of advanced virtual screening approaches.
Methods: In current study, we decided to use the crystal structures of 7WO3.pdb to propose effective inhibitors to inhibit the replication of the SARS-CoV-2 virus and, as a result, to effectively treat the disease of COVID-19. It seems that finding an inhibitor with suitable binding ability to SARS-CoV-2 3CLpro can lead to finding chemical structures with high ability to inhibit the replication and function of this virus. For this, after performing the validation phase on 59S ligand against SARS-CoV-2 3CLpro in 7WO3.pdb file, 82 chemical structures with structural similarity to 59S was screened from Pubchem data center and separately were docked to SARS-CoV-2 3CLpro coordination from 7WO3 PDB file and finally arranged based on the acquired ΔGbinding. In last step, essential pharmaceutical attributes of the three compounds with lowest ΔGbinding were also predicted using in silico tools.
Results: while the lowest ΔGbinding for 59S ligand was -6.8 kCal/mol, cyclo[Ala-Ala-Ala-N(Me)Tyr(Me)] with ΔGbinding=-8.2 kCal/mol; N-[5-[(3S,6R,9S)-3-butan-2-yl-6-[(4-methoxyphenyl)methyl]-2,5,8,11-tetraoxo-1,4,7,10-tetrazabicyclo[10.4.0]hexadecan-9-yl]pentyl]-N-hydroxyformamide) with ΔGbinding=-8.0 kCal/mol; and N-[5-[(3S,6R,9S,12R)-3-[(2R)-butan-2-yl]-6-[(4-methoxyphenyl)methyl]-2,5,8,11-tetraoxo-1,4,7,10-tetrazabicyclo[10.4.0]hexadecan-9-yl]pentyl]-N-hydroxyacetamide with ΔGbinding=-8.0 kCal/mol showed the lowest values between all of selected compounds. Also, computational based predicted attributes of the indicated compounds confirmed their potential to may use as efficient medicine.
Conclusion: Meanwhile, the use of virtual screening methods can be considered and used as an efficient and effective method to find strong and specific inhibitors of SARS-CoV-2 3CLpro. Such chemical structures with high affinity to SARS-CoV-2 3CLpro and acceptable pharmaceutical properties that inhibit the replication and function of the SARS-CoV-2 virus can eventually be considered as an option for the efficient and specific treatment of COVID-19.