Screening Inhibitory Potential of Anti-HIV RT RNA Aptamers

2013 ◽  
pp. 11-29 ◽  
Author(s):  
Margaret J. Lange ◽  
Donald H. Burke
Keyword(s):  
Rna Aptamers ◽  
Hiv Rt ◽  
Inhibitory Potential ◽  
Anti Hiv

scholarly journals Repurposing Multi-Targeting Plant Natural Product Scaffolds In Silico Against SARS-CoV-2 Non-Structural Proteins Implicated in Viral Pathogenesis

2021 ◽  
Author(s):  
Von Novi de Leon ◽  
Joe Anthony Manzano ◽  
Delfin Yñigo H. Pilapil ◽  
Rey Arturo T. Fernandez ◽  
James Kyle Ching ◽  
...  
Keyword(s):  
In Silico ◽  
Structural Proteins ◽  
Treatment Gap ◽  
Hiv Reverse Transcriptase ◽  
Pomolic Acid ◽  
Absorptive Property ◽  
Hiv Rt ◽  
Key Sites ◽  
Inhibitory Potential ◽  
Anti Hiv

<p>Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting <i>in silico</i> key sites in the structures of SARS-CoV-2 nsps. Moreover, structures of the anti-HIV compounds were considered for druggability and toxicity. 104 anti-HIV phytochemicals were subjected to molecular docking with papain-like protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-<i>O-</i>methyltransferase (nsp16) and its cofactor (nsp10), and endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top ten compounds per nsp were predicted using SwissADME. Their toxicity was also determined using OSIRIS Property Explorer.</p> <p>Results: Among the twenty-seven top-scoring compounds, the polyphenolic natural products amentoflavone (<b>1</b>), robustaflavone (<b>4</b>), punicalin (<b>9</b>), volkensiflavone (<b>11</b>), rhusflavanone (<b>13</b>), morelloflavone (<b>14</b>), hinokiflavone (<b>15</b>), and michellamine B (<b>19</b>) were multi-targeting and had the strongest affinities to at least two of the nsps (Binding Energy = -7.7 to -10.8 kcal/mol). Friedelin (<b>2</b>), pomolic acid (<b>5</b>), ursolic acid (<b>10</b>), garcisaterpenes A (<b>12</b>), hinokiflavone (<b>15</b>), and digitoxigenin-3-<i>O-</i>glucoside (<b>17</b>) were computationally druggable. Moreover, compounds <b>5</b> and <b>17</b> showed good gastrointestinal absorptive property. Most of the compounds were also predicted to be non-toxic.</p> <p>Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used as prototypes for anti-COVID-19 drug design.</p>

scholarly journals Repurposing Multi-Targeting Plant Natural Product Scaffolds In Silico Against SARS-CoV-2 Non-Structural Proteins Implicated in Viral Pathogenesis

2021 ◽  
Author(s):  
Von Novi de Leon ◽  
Joe Anthony Manzano ◽  
Delfin Yñigo H. Pilapil ◽  
Rey Arturo T. Fernandez ◽  
James Kyle Ching ◽  
...  
Keyword(s):  
In Silico ◽  
Structural Proteins ◽  
Treatment Gap ◽  
Hiv Reverse Transcriptase ◽  
Pomolic Acid ◽  
Absorptive Property ◽  
Hiv Rt ◽  
Key Sites ◽  
Inhibitory Potential ◽  
Anti Hiv

<p>Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting <i>in silico</i> key sites in the structures of SARS-CoV-2 nsps. Moreover, structures of the anti-HIV compounds were considered for druggability and toxicity. 104 anti-HIV phytochemicals were subjected to molecular docking with papain-like protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-<i>O-</i>methyltransferase (nsp16) and its cofactor (nsp10), and endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top ten compounds per nsp were predicted using SwissADME. Their toxicity was also determined using OSIRIS Property Explorer.</p> <p>Results: Among the twenty-seven top-scoring compounds, the polyphenolic natural products amentoflavone (<b>1</b>), robustaflavone (<b>4</b>), punicalin (<b>9</b>), volkensiflavone (<b>11</b>), rhusflavanone (<b>13</b>), morelloflavone (<b>14</b>), hinokiflavone (<b>15</b>), and michellamine B (<b>19</b>) were multi-targeting and had the strongest affinities to at least two of the nsps (Binding Energy = -7.7 to -10.8 kcal/mol). Friedelin (<b>2</b>), pomolic acid (<b>5</b>), ursolic acid (<b>10</b>), garcisaterpenes A (<b>12</b>), hinokiflavone (<b>15</b>), and digitoxigenin-3-<i>O-</i>glucoside (<b>17</b>) were computationally druggable. Moreover, compounds <b>5</b> and <b>17</b> showed good gastrointestinal absorptive property. Most of the compounds were also predicted to be non-toxic.</p> <p>Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used as prototypes for anti-COVID-19 drug design.</p>

scholarly journals 64. Broad-Spectrum Anti-HIV RT RNA Aptamers

2015 ◽  
Vol 23 ◽  
pp. S28
Author(s):  
Margaret J. Lange ◽  
Phuong D.M. Nguyen ◽  
Mackenzie K. Callaway ◽  
Donald H. Burke
Keyword(s):  
Broad Spectrum ◽  
Rna Aptamers ◽  
Hiv Rt ◽  
Anti Hiv

scholarly journals Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3821
Author(s):  
Rita Meleddu ◽  
Angela Corona ◽  
Simona Distinto ◽  
Filippo Cottiglia ◽  
Serenella Deplano ◽  
...  
Keyword(s):  
Single Agent ◽  
Hiv Reverse Transcriptase ◽  
Substitution Pattern ◽  
Associated Functions ◽  
Dual Inhibition ◽  
Hiv Rt ◽  
Therapeutic Protocols ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Selection Of

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (EMAC2063) was the most potent towards RNaseH (IC50 = 4.5 mM)- and RDDP (IC50 = 8.0 mM) HIV RT-associated functions.

scholarly journals A novel method for determining the inhibitory potential of anti-HIV drugs

2009 ◽  
Vol 30 (12) ◽  
pp. 610-616 ◽  
Author(s):  
Lin Shen ◽  
S. Alireza Rabi ◽  
Robert F. Siliciano
Keyword(s):  
Novel Method ◽  
Inhibitory Potential ◽  
Hiv Drugs ◽  
Anti Hiv

Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay

2020 ◽  
Vol 16 (7) ◽  
pp. 938-946 ◽  
Author(s):  
Mahdieh Safakish ◽  
Zahra Hajimahdi ◽  
Rouhollah Vahabpour ◽  
Rezvan Zabihollahi ◽  
Afshin Zarghi
Keyword(s):  
Molecular Modeling ◽  
Drug Target ◽  
Design Synthesis ◽  
Metal Chelating ◽  
Hydrophobic Site ◽  
Π Stacking Interaction ◽  
Molecular Modeling Studies ◽  
Inhibitory Potential ◽  
Anti Hiv ◽  
Hiv 1

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3’-end nucleotide as a streamlined metal chelating pharmacophore. Method: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone. Results: Molecular modeling studies revealed that amide functionality alongside oxadiazole heteroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupies hydrophobic site created by the cytidylate nucleotide (DC-16). Conclusion: The most potent and selective compound displayed 110 μM IC50 with a selectivity index of more than 2.

scholarly journals Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target

2015 ◽  
Vol 11 (12) ◽  
pp. e1005289 ◽  
Author(s):  
Dongsheng Li ◽  
Ting Wei ◽  
Daniel J. Rawle ◽  
Fangyun Qin ◽  
Rui Wang ◽  
...  
Keyword(s):  
Reverse Transcription ◽  
Specific Interaction ◽  
Hiv Rt ◽  
Anti Hiv ◽  
Hiv 1

ChemInform Abstract: A New Vinyl Selenone-Based Domino Approach to Spirocyclopropyl Oxindoles Endowed with anti-HIV RT Activity.

ChemInform ◽  
2016 ◽  
Vol 47 (24) ◽  
Author(s):  
M. Palomba ◽  
L. Rossi ◽  
L. Sancineto ◽  
E. Tramontano ◽  
A. Corona ◽  
...  
Keyword(s):  
Hiv Rt ◽  
Anti Hiv

scholarly journals Anti-HIV reverse transcriptase plant polyphenolic natural products with in silico inhibitory properties on seven non-structural proteins vital in SARS-CoV-2 pathogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Von Novi O. de Leon ◽  
Joe Anthony H. Manzano ◽  
Delfin Yñigo H. Pilapil ◽  
Rey Arturo T. Fernandez ◽  
James Kyle Anthony R. Ching ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Natural Products ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Structural Proteins ◽  
Hiv Reverse Transcriptase ◽  
Catalytic Sites ◽  
Key Sites ◽  
Inhibitory Potential ◽  
Anti Hiv

Abstract Background Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. This study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps. One hundred four anti-HIV phytochemicals were subjected to molecular docking with nsp3, 5, 10, 12, 13, 15, and 16. Top compounds in complex with the nsps were investigated further through molecular dynamics. The drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top compounds were also predicted using SwissADME. Their toxicity was likewise determined using OSIRIS Property Explorer. Results Among the top-scoring compounds, the polyphenolic functionalized natural products comprised of biflavones 1, 4, 11, 13, 14, 15; ellagitannin 9; and bisisoquinoline alkaloid 19 were multi-targeting and exhibited strongest binding affinities to at least two nsps (binding energy = − 7.7 to − 10.8 kcal/mol). The top ligands were stable in complex with their target nsps as determined by molecular dynamics. Several top-binding compounds were computationally druggable, showed good gastrointestinal absorptive property, and were also predicted to be non-toxic. Conclusions Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 non-structural proteins 3, 5, 10, 12, 13, 15, and 16. Our results highlight the importance of polyhydroxylated aromatic substructures for effective attachment in the binding/catalytic sites of nsps involved in post-translational mechanism pathways. As such with the nsps playing vital roles in viral pathogenesis, our findings provide inspiration for the design and discovery of novel anti-COVID-19 drug prototypes.

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