Investigation of the binding free energies of FDA approved drugs against subtype B and C-SA HIV PR: ONIOM approach

2017 ◽  
Vol 76 ◽  
pp. 77-85 ◽  
Author(s):  
Z.K. Sanusi ◽  
T. Govender ◽  
G.E.M. Maguire ◽  
S.B. Maseko ◽  
J. Lin ◽  
...  
Keyword(s):  
Free Energies ◽  
Subtype B ◽  
Approved Drugs ◽  
Oniom Approach ◽  
Fda Approved Drugs ◽  
Binding Free Energies

Comparison of the Molecular Dynamics and Calculated Binding Free Energies for Nine FDA-Approved HIV-1 PR Drugs Against Subtype B and C-SA HIV PR

2012 ◽  
Vol 81 (2) ◽  
pp. 208-218 ◽  
Author(s):  
Shaimaa M. Ahmed ◽  
Hendrik G. Kruger ◽  
Thirumala Govender ◽  
Glenn E. M. Maguire ◽  
Yasien Sayed ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energies ◽  
Subtype B ◽  
Hiv 1 ◽  
Binding Free Energies

scholarly journals Potential COVID-19 Protease Inhibitors: Repurposing FDAapproved Drugs

2020 ◽  
Author(s):  
Valentina Kouznetsova ◽  
David Huang ◽  
Igor F. Tsigelny
Keyword(s):  
Protease Inhibitors ◽  
Binding Pocket ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Free Energies ◽  
Inhibitor Binding ◽  
Approved Drugs ◽  
Docking Interaction ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

Using as a template the crystal structure of COVID-19 protease, we developed a pharmacophore of functional centers of the protease inhibitor-binding pocket. Then we conducted data mining of the conformational database of FDA-approved drugs. This search brought 64 compounds that can be potential inhibitors of COVID-19 protease. The conformations of these compounds undergone 3D fingerprint similarity clusterization. Then we conducted docking of possible conformers of these drugs to the binding pocket of protease. We also conducted the same docking of random compounds. Free energies of the docking interaction for the selected compounds were clearly lower than random compounds. Three of the selected compounds were carfilzomib, cyclosporine A, and azithromycin—the drugs that already are tested for COVID-19 treatment. Among the selected compounds are two HIV protease inhibitors and two hepatitis C protease inhibitors. We recommend testing of the selected compounds for treatment of COVID-19.<br><br>

scholarly journals Potential COVID-19 papain-like protease PLpro inhibitors: repurposing FDA-approved drugs

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9965 ◽  
Author(s):  
Valentina L. Kouznetsova ◽  
Aidan Zhang ◽  
Mahidhar Tatineni ◽  
Mark A. Miller ◽  
Igor F. Tsigelny
Keyword(s):  
Crystal Structure ◽  
Pharmacophore Model ◽  
Binding Pocket ◽  
Free Energies ◽  
Inhibitor Binding ◽  
Drug List ◽  
Approved Drugs ◽  
Docking Interaction ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

Using the crystal structure of SARS-CoV-2 papain-like protease (PLpro) as a template, we developed a pharmacophore model of functional centers of the PLpro inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search identified 147 compounds that can be potential inhibitors of SARS-CoV-2 PLpro. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding pocket of PLpro. Docking of random compounds to the binding pocket of protease was also done for comparison. Free energies of the docking interaction for the selected compounds were lower than for random compounds. The drug list obtained includes inhibitors of HIV, hepatitis C, and cytomegalovirus (CMV), as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy. We recommend testing of the selected compounds for treatment of COVID-19

scholarly journals Potential COVID-19 Protease Inhibitors: Repurposing FDAapproved Drugs

2020 ◽  
Author(s):  
Valentina Kouznetsova ◽  
David Huang ◽  
Igor F. Tsigelny
Keyword(s):  
Protease Inhibitors ◽  
Binding Pocket ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Free Energies ◽  
Inhibitor Binding ◽  
Approved Drugs ◽  
Docking Interaction ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

Using as a template the crystal structure of COVID-19 protease, we developed a pharmacophore of functional centers of the protease inhibitor-binding pocket. Then we conducted data mining of the conformational database of FDA-approved drugs. This search brought 64 compounds that can be potential inhibitors of COVID-19 protease. The conformations of these compounds undergone 3D fingerprint similarity clusterization. Then we conducted docking of possible conformers of these drugs to the binding pocket of protease. We also conducted the same docking of random compounds. Free energies of the docking interaction for the selected compounds were clearly lower than random compounds. Three of the selected compounds were carfilzomib, cyclosporine A, and azithromycin—the drugs that already are tested for COVID-19 treatment. Among the selected compounds are two HIV protease inhibitors and two hepatitis C protease inhibitors. We recommend testing of the selected compounds for treatment of COVID-19.<br><br>

Comparing the Metabolome of a Caribbean Sponge to 420 FDA Approved Drugs, a Molecular Networking Approach

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
H Houson ◽  
J Schlesser ◽  
J Beverage ◽  
V Macherla ◽  
E Esquenazi
Keyword(s):  
Molecular Networking ◽  
Approved Drugs ◽  
Fda Approved Drugs

Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  
Keyword(s):  
Day Treatment ◽  
Treatment Options ◽  
Developed Countries ◽  
Methyl Transferase ◽  
Comt Inhibitors ◽  
Mao B ◽  
Pharmacokinetic Properties ◽  
Us Fda ◽  
Approved Drugs ◽  
Fda Approved Drugs

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

2018 ◽  
Vol 15 (2) ◽  
pp. 208-220 ◽  
Author(s):  
Vaibhav Mishra ◽  
Tejpal Singh Chundawat
Keyword(s):  
Bond Formation ◽  
Catalyst Design ◽  
Biologically Active ◽  
Reaction Conditions ◽  
Biological Targets ◽  
Amination Reaction ◽  
Drug Synthesis ◽  
Substituted Piperazine ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

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