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Docking Analysis of 07 Anti-HCV Drugs with COVID-19 Main Protease PDB ID: 6LU7

A Ajeet*, Babita Aggarwal, Santosh Kumar Verma, Ajeet Singh

Faculty of Pharmaceutical Sciences, Motherhood University, Roorkee, India

Abstract: 07 anti-HCV drugs have been processed and observed by docking analysis for understanding the binding patteren of drugs with COVID-19 main protease PDB ID: 6LU7 for any possibilities of protease inhibition. For docking analysis PyRx- Python Prescription 0.8 was used. This analysis reveals that the essential amino acids involved in binding of anti-HCV drugs to COVID-19 main protease PDB ID: 6LU7 are Threonine (THR), Cysteine (CYS), Histidine (HIS), Methionine (MET) and Proline (PRO). After docking analysis it was observed that Ledipasvir may be act as COVID-19 main protease inhibitor despite of being anti-HCV and may further be used in the treatment of COVID-19 infection after having proper clinical proofs.

Keywords: COVID-19, anti-HCV, protease inhibition

Received June 07, 2020; Revised June 15, 2020; Accepted June 21, 2020

Citation: A Ajeet, Babita Aggarwal, Santosh Kumar Verma, Ajeet Singh, Docking Analysis of 07 Anti-HCV Drugs with COVID-19 Main Protease PDB ID: 6LU7. American Journal of Pharmacological Sciences, 8 (2). 21-25. January 2020. doi:10.12691/ajps-8-2-1

1. Introduction

Corona virus is well known threat peaking its crown again to world in the form of nCoV-19 (COVID-19) during the current time which was initially supposed to be emerged several years ago in different other forms like Middle East Respiratory Syndrome-Corona-Virus (MERS-CoV) and Severe Acute Respiratory Syndrome-corona-virus (SARS-CoV) with the few similar pathological symptoms but with great power of spreading infection to one another. [1] There is an option out of many for management of virus is known as inhibition of RNA dependent RNA protease (RdRp) enzyme in virus for cessation of viral replication. [2] Hence, to contribute a little with some possibilities of inhibition of RNA dependent RNA protease (RdRp) enzyme of COVID-19 virus by existing anti-HCV drugs; we have screened 7 anti-HCV drugs which were already approved and tested against their pharmacokinetic, pharmacodynamic and toxicity parameters; for studying their molecular interaction with recently deposited and released crystal structure of COVID-19 main protease (viral protein) with Protein Data Bank (PDB) ID: 6LU7. [3] The drug molecules which were used in this study are Daclatasvir (Hepatitis C virus (HCV) NS5A replication complex inhibitor) [4], Dasabuvir (It emerges as medical advance when used as a combination therapy for HCV) [5], Elbasvir [6], Ledipasvir [7], Lomibuvir [8], Ombitasvir [9] and Paritaprevir [10].

To study this interaction between pre-established anti-HCV drugs and crystal structure of COVID-19 main protease we have used docking analysis. [11,12,13,14]

2. Materials and Methods

2.1. Data, Database, and Tools

For carrying out this study, National Center for Bio-technology Information’s (NCBI) website and Protein Data Bank’s (PDB) website were used as biological and chemical data sources. For designing and optimizing the geometry of the derivatives, ChemDraw Ultra 10.0 [11,15]. Co-crystallized 3D structure of COVID-1 main protease; PDB ID: 6LU7 (viral protein) was downloaded from Protein Data Bank.

2.2. Docking

The docking analysis of 07 anti-HCV drugs and inhibitor N3 complexes within 3D structure of COVID-19 main protease; PDB ID: 6LU7 was performed by PyRx- Python Prescription 0.8.

PyRx is Virtual Screening software for Computational Drug Discovery that can be used to screen libraries of compounds against potential drug targets. PyRx enables Medicinal Chemists to run Virtual Screening from any platform and helps users in every step of this process - from data preparation to job submission and analysis of the results.

3. Results and Discussion

07 anti-HCV drug molecules were processed for virtual screening via docking studies. All the molecules were analyzed for their binding characteristics such as binding residues (Amino Acid: AA), number of hydrogen bonds, binding atoms with type of bonds. All these observed characteristics are given in Table 1 to Table 16 and clicked photographs of molecular interactions are given in Figure 1.

Table 1. Daclatasvir- Hydrophobic Interactions

Table 2. Daclatasvir- Hydrogen Bonds Interaction

Table 3. Dasabuvir - Hydrophobic Interactions

Table 4. Dasabuvir -Hydrogen Bonds Interaction

Table 5. Elbasvir -Hydrophobic Interactions

Table 6. Elbasvir -Hydrogen Bonds Interaction

Table 7. Ledipasvir -Hydrophobic Interactions

Table 8. Ledipasvir -Hydrogen Bonds Interactions

Table 9. Lomibuvir -Hydrophobic Interactions

Table 10. Lomibuvir- Hydrogen Bonds Interactions

Table 11. Ombitasvir- Hydrophobic Interactions

Table 12. Ombitasvir - Hydrogen Bonds Interactions

Table 13. Paritaprevir - Hydrophobic Interactions

Table 14. Paritaprevir - Hydrogen Bonds Interactions

Table 15. N3 Reference molecule- Hydrophobic Interactions

Table 16. N3 Reference molecule- Hydrogen Bond Interaction

Figure 1. Docked images of anti-HCV drugs taken and ref. drug complexes in COVID-19 main protease 6LU7

Table 17. Residual analysis of docked anti-HCV drugs

Binding Amino acids analysis has been performed. This comparative analysis was performed with the residues of inhibitor N3 complexes within 3D structure of COVID-19 main protease; PDB ID: 6LU7. This analysis is given in Table 17.

On analyzing Table 17, it was observed that Amino acids or residues which plays key role in binding of reference molecule N3 are THR (Threonine), HIS (Histidine), CYS (Cystein), MET (Methionine) and PRO (Proline)

Anti-HCV drugs Dasabuvir (associated amino acid is- PRO; No. of hydrogen bonds- 1), Ledipasvir (associated amino acids are- THR & MET; No. of hydrogen bonds- 5) and Ombitasvir (associated amino acid is- THR; No. of hydrogen bonds- 6) were found to be very close to the binding pocket of protein 6LU7.

4. Conclusions

Ledipasvir has shown its possibilities of having inhibition of COVID-19 main protease enzyme; this enzyme is responsible for replication of virus in living body. To reach this conclusion we have completed a journey of docking analysis of 07 well known anti-HCV drugs with COVID-19 main protease PDB ID: 6LU7. Docking was performed with the help of PyRx- Python Prescription 0.8 and the results were observed and analyzed; which screened 3 (Dasabuvir, Ledipasvir and Ombitasvir) out of 07 anti-HCV drugs having possibilities of protease inhibition of virus. Further residual analysis showed that Ledipasvir may have probabilities of protease inhibition for cessation of viral replication as amino acids of binding pocket (THR & MET out of 5 amino acids) were similar to reference molecule N3 complexes within 3D structure of COVID-19 main protease 6LU7. These results primarily showed the possibilities only although clinical studies are still required to ascertain the findings.

Funding

This research received no external funding.

Acknowledgments

Authors are thankful to CBBE (Computational Biology for Biochemical Experiments, ), In-silico Drug Design and Development Services, India, for docking and cross analysing the data.

Conflicts of Interest

The authors declare no conflict of interest.

References

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[13]   | Ajeet. In silico designing and characterization of Amiloride derivatives as ion channel modulator. Med Chem Res. 2013, 22, 1004-1010.
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