scholarly journals RNA–protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers

2017 ◽  
Vol 45 (10) ◽  
pp. 6087-6097 ◽  
Author(s):  
Margaret J. Lange ◽  
Phuong D. M. Nguyen ◽  
Mackenzie K. Callaway ◽  
Marc C. Johnson ◽  
Donald H. Burke
2018 ◽  
Vol 19 (10) ◽  
pp. 3231 ◽  
Author(s):  
Aleksandra Dąbrowska ◽  
Tomasz Pieńko ◽  
Przemysław Taciak ◽  
Katarzyna Wiktorska ◽  
Zdzisław Chilmonczyk ◽  
...  

Here we present new derivatives of nucleoside reverse transcriptase inhibitors with a C20 fullerene. The computational chemistry methods used in this study evaluate affinity of designed compounds towards the HIV-1 reverse transcriptase (RT) binding site and select the most active ones. The best of the designed compounds have superior or similar affinity to RT active site in comparison to most active test compounds, including drugs used in anti-HIV therapy.


1995 ◽  
Vol 6 (4) ◽  
pp. 217-221 ◽  
Author(s):  
J. M. Cherrington ◽  
S. J. W. Allen ◽  
N. Bischofberger ◽  
M. S. Chen

The inhibitory effects of the diphosphates of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its analogues on HIV reverse transcriptase and human DNA polymerases α, β, and γ have been studied. The analogues investigated are the diphosphates of 9-(2-phosphonylmethoxypropyl)adenine (PMPApp), 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAPpp), and (2R,5R)-9-[2,5-dihydro-5-(phosphonyl methoxy)-2-furanyl]adenine (D4APpp). These four compounds are much more inhibitory to HIV reverse transcriptase when an RNA template rather than a DNA template is used. The Ki, values for the four compounds range from 11 to 22 nM with an RNA template. The Ki, values for ddCTP and AZTTP are 54 nM and 8 nM, respectively. PMEApp and its analogues show varying degrees of inhibition of the human DNA polymerases. The Ki, values for PMEApp, PMPApp and PMPDAPpp against DNA polymerase α are in the micromolar range, while D4APpp is a poor inhibitor of this enzyme with a Ki, value of 65.9 μM. The inhibition of DNA polymerase β by PMEApp, PMPApp and D4APpp is minimal, while PMPDAPpp shows higher inhibition of DNA polymerase β with a Ki, value of 9.71 μM. The Ki, values for PMEApp and D4APpp against DNA polymerase γ are submicromolar, while PMPApp and PMPDAPpp are much less inhibitory to this enzyme. For comparison, ddCTP was found to be a more potent inhibitor of DNA polymerases β and γ than the diphosphates of PMEA and its analogues.


Author(s):  
Von Novi O. de Leon ◽  
Joe Anthony H. Manzano ◽  
Delfin Yñigo H. Pilapil ◽  
Rey Arturo T. Fernandez ◽  
James Kyle Anthony R. Ching ◽  
...  

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.


2021 ◽  
Vol 6 (3) ◽  
pp. p26
Author(s):  
Silas David Emmanuel ◽  
I. M. Bugaje ◽  
S. M. Mohammmad

Purposes: The unprecedented and sequence through which an estimate of 25 million lives have gone to their early grave yard through Acquired Immune-deficiency Syndrome HIV/AIDS can never be quantified; since, when it was first describes in 1981. In 2017/2018 by (UNAIDS) it was estimated globally for about 36.9millions people were living with Human, Immunodeficiency Virus (HIV) so to say. Henceforth the progress made in the field of treatment in the form of Antiretroviral Therapy (ART) disease has not been fully ascertain for the cure of HIV/AIDS; except, perpetual clinical suppressions. Thus, the current challenges that man kinds faces with the used of perpetual intake of antiretroviral therapy (clinical suppression)/artificial vaccine is un-justifiable. However, search for HIV therapy have open a new chapter in the search for novel drugs from Kaduna Polytechnic procedure. This review focuses on vitamins, antioxidant, mineral and supplement as sources of in-hibitors or eradications for human immunodeficiency virus type-1 (HIV) reverse transcriptase. Objective: To assess whether vitamins, antioxidant, minerals supplement are effective and safe in eradicating mortality and morbidity among populace with HIV infection. Selection criteria: Randomized control trials were selected that compared the effect of vitamins (A, C, D, E, K,), antioxidant, minerals and supplement with regard to treatment measures in HIV infected persons. Methods: To prevent authors bias, based on a systematic search of literature; anti-HIV reverse transcriptase activity of some plant’s species like those of Eucalyptus leaves, Garlic fresh fruits, Baobab leaves, aloe vera, neem leaves, moringa leaves, bitter leaves etc. respectively. Thus, these medicinal plants contain an appreciable or above values antioxidant compound or photochemical like those of Phenolic, anthraquinone, tannin, falconoid, terpenoid, lignin, coumarins etc. respectively. Contrarywise, these phytochemical compounds have been exploited traditionally for the cure of many diseases as well as inhibition of viral replication/transcription. Further investigations have shared more light through which phytochemicals compounds inhibit virus replication either during the viral entry inside the host cell or during their replication. Originality: in view of the current investigation or to accelerate drug discovery and innovation, this review recommends the urgent need to tap into the enrich locally available endogenous knowledge of putative anti- HIV/AIDS, photochemical and their derivatives, (reverse pharmacology, determine pan assay, interferences compounds, microbial enzyme metabolites relationship and their mechanisms to treat virial diseases.


2008 ◽  
Vol 18 (3) ◽  
pp. 1120-1123 ◽  
Author(s):  
Constantine G. Boojamra ◽  
Richard L. Mackman ◽  
David Y. Markevitch ◽  
Vidya Prasad ◽  
Adrian S. Ray ◽  
...  

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