This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Naruka Solomon Yakubu
University of Jos
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9066-8757
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This work is licensed under a CC BY 4.0 License. Read Full License
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Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Computer-aided drug design has been an effective strategy and approach to discover, develop, analyze, accelerate and economize design and development of drugs and biologically active molecules. A total of twelve analogues of chloroquine (CQ) and hydroxychloroquine (HCQ) were designed and virtually analyzed using PyRx software, Molinspiration, Swiss ADME, Swiss-Target Prediction software and ProTox-II-Prediction of toxicity platform. Based on the docking studies carried out using Autodock vina, five analogues; H-368 (-6.0 Kcal/mol), H-372 (--6.0 Kcal/mol), H-156 (-5.9 Kcal/mol), H-139 (-5.7 Kcal/mol), C-136 (-5.7 Kcal/mol) exhibited higher binding affinity compared to HCQ(-5.5 Kcal/mol), while all twelve analogues exhibited higher binding affinity compared to CQ (-4.5Kcal/mol). In silico analysis of toxicity profile of this analogues shows a lower potential to toxicity and a comparable activity on some major isoforms of cytochrome P450. But unlike the parent molecules, both H-139 and H-156 are substrates of P-glycoproteins (P-gp) which implies that these analogues possess high clearance and less pharmacokinetic-related drug-drug interactions compared to the parent molecules. Herein we propose these analogues as potential inhibitors or lead compounds against the coronavirus with a view of conducting more molecular dynamic simulations, synthesizing and conducting in vitro studies on them.
Keywords
COVID-19, SARS-CoV-2, Docking, Chloroquine, Hydroxychloroquine
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Naruka Solomon Yakubu
University of Jos
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9066-8757
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 08 Jul, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Drug Discovery, Design, & Development
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Computer-aided drug design has been an effective strategy and approach to discover, develop, analyze, accelerate and economize design and development of drugs and biologically active molecules. A total of twelve analogues of chloroquine (CQ) and hydroxychloroquine (HCQ) were designed and virtually analyzed using PyRx software, Molinspiration, Swiss ADME, Swiss-Target Prediction software and ProTox-II-Prediction of toxicity platform. Based on the docking studies carried out using Autodock vina, five analogues; H-368 (-6.0 Kcal/mol), H-372 (--6.0 Kcal/mol), H-156 (-5.9 Kcal/mol), H-139 (-5.7 Kcal/mol), C-136 (-5.7 Kcal/mol) exhibited higher binding affinity compared to HCQ(-5.5 Kcal/mol), while all twelve analogues exhibited higher binding affinity compared to CQ (-4.5Kcal/mol). In silico analysis of toxicity profile of this analogues shows a lower potential to toxicity and a comparable activity on some major isoforms of cytochrome P450. But unlike the parent molecules, both H-139 and H-156 are substrates of P-glycoproteins (P-gp) which implies that these analogues possess high clearance and less pharmacokinetic-related drug-drug interactions compared to the parent molecules. Herein we propose these analogues as potential inhibitors or lead compounds against the coronavirus with a view of conducting more molecular dynamic simulations, synthesizing and conducting in vitro studies on them.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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