In silico based unraveling of New Delhi metallo-β-lactamase (NDM-1) inhibitors from natural compounds: a molecular docking and molecular dynamics simulation study

Background & Objectives The massive outbreak of Novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has turned out to be a serious global health issue worldwide. Currently, no drugs or vaccines are available for the treatment of COVID-19. The current computational study was attempted to identify a novel therapeutic inhibitor against novel SARS-CoV-2 using in silico drug discovery pipeline. Methods In the present study, the human angiotensin-converting enzyme 2 (ACE2) receptor was the target for the designing of drugs against the deadly virus. The 3D structure of the receptor was modeled & validated using a Swiss-model, Procheck & Errat server. A molecular docking study was performed between a group of natural & synthetic compounds having proven anti-viral activity with ACE2 receptor using Autodock tool 1.5.6. The molecular dynamics simulation study was performed using Desmond v 12 to evaluate the stability and interaction of the ACE2 receptor with a ligand. Results Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (−5.20 kcal/mol), thymoquinone (−4.71 kcal/mol), and andrographolide (Kalmegh) (−4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor. The bioactivity and drug-likeness properties of compounds show their better pharmacological property and safer to use. Interpretation & Conclusions The study concludes the high potential of cinnamic acid, thymoquinone, and andrographolide against the SARS-CoV-2 ACE2 receptor protein. Thus, the molecular docking and MD simulation study will aid in understanding the molecular interaction between ligand and receptor binding site, thereby leading to novel therapeutic intervention.

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Molecular docking analysis and molecular dynamics simulation study of ameltolide analogous as a sodium channel blocker

TURKISH JOURNAL OF CHEMISTRY ◽

10.3906/kim-1402-37 ◽

2015 ◽

Vol 39 ◽

pp. 306-316 ◽

Cited By ~ 4

Author(s):

Maryam IMAN ◽

Atefeh SAADABADI ◽

Asghar DAVOOD

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Sodium Channel ◽

Simulation Study ◽

Channel Blocker ◽

Dynamics Simulation ◽

Sodium Channel Blocker ◽

Docking Analysis ◽

Molecular Docking Analysis

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Potential charge transfer probe induced conformational changes of model plasma protein human serum albumin: Spectroscopic, molecular docking, and molecular dynamics simulation study

Biopolymers ◽

10.1002/bip.22057 ◽

2012 ◽

Vol 97 (10) ◽

pp. 766-777 ◽

Cited By ~ 16

Author(s):

Sankar Jana ◽

Sasanka Dalapati ◽

Shalini Ghosh ◽

Nikhil Guchhait

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Charge Transfer ◽

Molecular Dynamics Simulation ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Simulation Study ◽

Dynamics Simulation

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Molecular dynamics simulation study and molecular docking descriptors in structure-based QSAR on acetylcholinesterase (AChE) inhibitors

SAR and QSAR in Environmental Research ◽

10.1080/1062936x.2013.792877 ◽

2013 ◽

Vol 24 (9) ◽

pp. 773-794 ◽

Cited By ~ 19

Author(s):

S. Gharaghani ◽

T. Khayamian ◽

M. Ebrahimi

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Simulation Study ◽

Dynamics Simulation ◽

Ache Inhibitors

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A mechanistic approach to explore novel HDAC1 inhibitor using pharmacophore modeling, 3D- QSAR analysis, molecular docking, density functional and molecular dynamics simulation study

Journal of Molecular Graphics and Modelling ◽

10.1016/j.jmgm.2016.09.008 ◽

2016 ◽

Vol 70 ◽

pp. 54-69 ◽

Cited By ~ 9

Author(s):

Sanjay K. Choubey ◽

Jeyakanthan Jeyaraman

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Simulation Study ◽

Density Functional ◽

3D Qsar ◽

Pharmacophore Modeling ◽

Dynamics Simulation ◽

Qsar Analysis ◽

Mechanistic Approach

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Identification of potential carboxylic acid-containing drug candidate to design novel competitive NDM inhibitors: An in-silico approach comprising combined virtual screening and molecular dynamics simulation

10.1101/2021.07.05.451101 ◽

2021 ◽

Author(s):

Anand Anbarasu ◽

Balaji Veeraraghavan ◽

Karthick Vasudevan ◽

Soumya Basu ◽

Amala Arumugam ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Carboxylic Acid ◽

In Silico ◽

Hydrolytic Activity ◽

Dynamics Simulation ◽

Drug Candidate ◽

New Delhi ◽

Beta Lactamase ◽

Simulation Studies

Metallo-β-lactamases (MBLs) producing bacteria especially the ones with New Delhi metallo-beta-lactamase-1 (NDM-1) and its variants can potentially hydrolyse all the major β-lactam antibiotics, ultimately escalating anti-microbial resistance world-wide. There is a dearth of approved inhibitors to combat NDM and other MBLs producing bacteria. Hence we focussed to find novel inhibitor(s) in-silico which can potentially suppress the activity of NDM/ MBLs. 2400 compounds were virtually screened to identify a promising carboxylic acid-containing compound (CID-53986787) analogous to NDM antagonist Captopril. Our lead compound can bind adjacent to the active site zinc ions (Zn1 and Zn2) in all highly resistant NDM variants. CID-53986787 possesses ~5-8% higher binding affinity than Captopril, exhibiting molecular interactions with crucial residues that can destabilize the hydrolytic activity of NDM. CID-53986787 was virtually evaluated to ascertain its safe pharmacological/ toxicity profile. Molecular dynamics simulation studies elucidated its stable interaction with the target protein (NDM-1).

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