Abstract
Background: Hepatitis C Virus (HCV) infection is a major public health concern across the globe. At present, direct-acting antivirals are the treatment of choice. However, the long-term effect of this therapy has yet to be ascertained. Previously, fluoroquinolones have been reported to inhibit HCV replication by targeting NS3 protein. Therefore, it is logical to hypothesize that the natural analogs of fluoroquinolones will exhibit NS3 inhibitory activity with substantially lesser side effects. Method: In this study, we tested the application of a recently devised integrated in-silico Cheminformatics-Molecular Docking approach to identify physicochemically similar natural analogs of fluoroquinolones from the available databases (Ambinter, Analyticon, Indofines, Specs, and TimTec). Molecular docking and ROC curve analyses were performed, using PatchDock and Graphpad software, respectively, to compare and analyze drug-protein interactions between active natural analogs, Fluoroquinolones, and HCV NS3 protein. Result: In our analysis, we were able to shortlist 18 active natural analogs, out of 10,399, that shared physicochemical properties with the template drugs (fluoroquinolones). These analogs showed comparable binding efficacy with fluoroquinolones in targeting 32 amino acids in the HCV NS3 active site that are crucial for NS3 activity. Our approach had around 80 % sensitivity and 70 % specificity in identifying physicochemically similar analogs of fluoroquinolones. Conclusion: Our current data suggest that our approach can be efficiently applied to identify putative HCV drug inhibitors that can be taken for in vitro testing. This approach can be applied to discover physicochemically similar analogs of virtually any drug, thus providing a speedy and inexpensive approach to complement drug discovery and design, which can tremendously economize on time and money spent on the screening of putative drugs.
| Original language | English |
|---|---|
| Article number | 107167 |
| Journal | Computational Biology and Chemistry |
| Volume | 84 |
| DOIs | |
| Publication status | Published - Feb 2020 |
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Keywords
- Antiviral agents
- Cheminformatics
- Drug discovery
- Molecular docking
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Organic Chemistry
- Computational Mathematics
Cite this
Application of an integrated cheminformatics-molecular docking approach for discovery for physicochemically similar analogs of fluoroquinolones as putative HCV inhibitors. / Anwar, Muhammad Faraz; Khalid, Ramsha; Hasanain, Alina; Naeem, Sadaf; Zarina, Shamshad; Abidi, Syed Hani; Ali, Syed.
In: Computational Biology and Chemistry, Vol. 84, 107167, 02.2020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Application of an integrated cheminformatics-molecular docking approach for discovery for physicochemically similar analogs of fluoroquinolones as putative HCV inhibitors
AU - Anwar, Muhammad Faraz
AU - Khalid, Ramsha
AU - Hasanain, Alina
AU - Naeem, Sadaf
AU - Zarina, Shamshad
AU - Abidi, Syed Hani
AU - Ali, Syed
PY - 2020/2
Y1 - 2020/2
N2 - Background: Hepatitis C Virus (HCV) infection is a major public health concern across the globe. At present, direct-acting antivirals are the treatment of choice. However, the long-term effect of this therapy has yet to be ascertained. Previously, fluoroquinolones have been reported to inhibit HCV replication by targeting NS3 protein. Therefore, it is logical to hypothesize that the natural analogs of fluoroquinolones will exhibit NS3 inhibitory activity with substantially lesser side effects. Method: In this study, we tested the application of a recently devised integrated in-silico Cheminformatics-Molecular Docking approach to identify physicochemically similar natural analogs of fluoroquinolones from the available databases (Ambinter, Analyticon, Indofines, Specs, and TimTec). Molecular docking and ROC curve analyses were performed, using PatchDock and Graphpad software, respectively, to compare and analyze drug-protein interactions between active natural analogs, Fluoroquinolones, and HCV NS3 protein. Result: In our analysis, we were able to shortlist 18 active natural analogs, out of 10,399, that shared physicochemical properties with the template drugs (fluoroquinolones). These analogs showed comparable binding efficacy with fluoroquinolones in targeting 32 amino acids in the HCV NS3 active site that are crucial for NS3 activity. Our approach had around 80 % sensitivity and 70 % specificity in identifying physicochemically similar analogs of fluoroquinolones. Conclusion: Our current data suggest that our approach can be efficiently applied to identify putative HCV drug inhibitors that can be taken for in vitro testing. This approach can be applied to discover physicochemically similar analogs of virtually any drug, thus providing a speedy and inexpensive approach to complement drug discovery and design, which can tremendously economize on time and money spent on the screening of putative drugs.
AB - Background: Hepatitis C Virus (HCV) infection is a major public health concern across the globe. At present, direct-acting antivirals are the treatment of choice. However, the long-term effect of this therapy has yet to be ascertained. Previously, fluoroquinolones have been reported to inhibit HCV replication by targeting NS3 protein. Therefore, it is logical to hypothesize that the natural analogs of fluoroquinolones will exhibit NS3 inhibitory activity with substantially lesser side effects. Method: In this study, we tested the application of a recently devised integrated in-silico Cheminformatics-Molecular Docking approach to identify physicochemically similar natural analogs of fluoroquinolones from the available databases (Ambinter, Analyticon, Indofines, Specs, and TimTec). Molecular docking and ROC curve analyses were performed, using PatchDock and Graphpad software, respectively, to compare and analyze drug-protein interactions between active natural analogs, Fluoroquinolones, and HCV NS3 protein. Result: In our analysis, we were able to shortlist 18 active natural analogs, out of 10,399, that shared physicochemical properties with the template drugs (fluoroquinolones). These analogs showed comparable binding efficacy with fluoroquinolones in targeting 32 amino acids in the HCV NS3 active site that are crucial for NS3 activity. Our approach had around 80 % sensitivity and 70 % specificity in identifying physicochemically similar analogs of fluoroquinolones. Conclusion: Our current data suggest that our approach can be efficiently applied to identify putative HCV drug inhibitors that can be taken for in vitro testing. This approach can be applied to discover physicochemically similar analogs of virtually any drug, thus providing a speedy and inexpensive approach to complement drug discovery and design, which can tremendously economize on time and money spent on the screening of putative drugs.
KW - Antiviral agents
KW - Cheminformatics
KW - Drug discovery
KW - Molecular docking
UR - http://www.scopus.com/inward/record.url?scp=85076353500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076353500&partnerID=8YFLogxK
U2 - 10.1016/j.compbiolchem.2019.107167
DO - 10.1016/j.compbiolchem.2019.107167
M3 - Article
AN - SCOPUS:85076353500
VL - 84
JO - Computational Biology and Chemistry
JF - Computational Biology and Chemistry
SN - 1476-9271
M1 - 107167
ER -