scholarly journals Efficient repositioning of approved drugs as anti-HIV agents using Anti-HIV-Predictor

2016 ◽  
Author(s):  
Shao-Xing Dai ◽  
Huan Chen ◽  
Wen-Xing Li ◽  
Yi-Cheng Guo ◽  
Jia-Qian Liu ◽  
...  
Keyword(s):  
Web Server ◽  
Female Infertility ◽  
Hiv Therapy ◽  
Link Type ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Syncytia Formation ◽  
Anti Hiv Agents ◽  
Anti Hiv

AbstractDevelopment of new, effective and affordable drugs against HIV is urgently needed. In this study, we developed a world’s first web server called Anti-HIV-Predictor (http://bsb.kiz.ac.cn:70/hivpre) for predicting anti-HIV activity of given compounds. This server is rapid and accurate (accuracy >93% and AUC > 0.958). We applied the server to screen 1835 approved drugs for anti-HIV therapy. Totally 67 drugs were predicted to have anti-HIV activity, 25 of which are anti-HIV drugs. Then we experimentally evaluated 35 predicted new anti-HIV compounds by assays of syncytia formation, p24 quantification, cytotoxicity. Finally, we repurposed 7 approved drugs (cetrorelix, dalbavancin, daunorubicin, doxorubicin, epirubicin, idarubicin and valrubicin) as new anti-HIV agents. The original indication of these drugs is involved in a variety of diseases such as female infertility and cancer. Anti-HIV-Predictor and the 7 repurposed anti-HIV agents provided here demonstrate the efficacy of this strategy for discovery of new anti-HIV agents.

scholarly journals Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs

2008 ◽  
Vol 52 (6) ◽  
pp. 2111-2119 ◽  
Author(s):  
Hirotomo Nakata ◽  
Seth M. Steinberg ◽  
Yasuhiro Koh ◽  
Kenji Maeda ◽  
Yoshikazu Takaoka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Synergistic Effects ◽  
Immunodeficiency Virus ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Nonparametric Statistical ◽  
Anti Hiv ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1Ba-L and a 50:50 mixture of R5-HIV-1Ba-L and X4-HIV-1ERS104pre (HIV-1Ba-L/104pre) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1Ba-L/104pre when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors.

Pyrazole Containing Anti-HIV Agents: An Update

2022 ◽  
Vol 18 ◽  
Author(s):  
Sanjay Kumar ◽  
Shiv Gupta ◽  
Varsha Rani ◽  
Priyanka Sharma
Keyword(s):  
Review Article ◽  
Pyrazole Derivatives ◽  
Therapeutic Activity ◽  
Pharmacological Activities ◽  
Drug Discovery And Development ◽  
The World ◽  
Hiv Drugs ◽  
Anti Hiv Agents ◽  
Comprehensive Compilation ◽  
Anti Hiv

Background: Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer, antidepressant, anti-inflammatory, antibacterial, etc. Additionally, the pyrazole moiety has shown potent anti-HIV activity as a core heterocycle or substituted heterocycles derivatives (mono, di, tri, tetra, and fused pyrazole derivatives). To assist the development of further potential anti-HIV agents containing pyrazole nucleus, here we have summarized pyrazole containing anti-HIV compounds that have been reported by researchers all over the world for the last two decades. Objective: The present review concentrates on an assortment of pyrazole containing compounds, particularly for potential therapeutic activity against HIV. Methods: Google Scholar, Pubmed, and SciFinder were searched databases with ‘‘pyrazol’’ keywords. Further, the year of publication and keywords ‘‘Anti-HIV’’ filter was applied to obtain relevant reported literature for anti-HIV agents containing pyrazole as a core or substituted derivatives. Results: This review article has shown the comprehensive compilation of 220 compounds containing pyrazole nucleus and possessing anti-HIV activity by sorting approximately 40 research articles from 2001 to date. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (13), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (31), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (88), 3-cyanophenoxypyrazole derivative (130), and 4-(4-chlorophenyl)-5-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)-3-phenyl-5,6-dihydro-4H-pyrazolo[4,3-d]isoxazole (178) were the most potent mono-, di-, tri-, tetra-substituted, and fused pyrazole derivatives, respectively, which have shown potent anti-HIV activity among all the described derivatives as compared with standard anti-HIV drugs. Conclusion: This review article provides an overview of the potential therapeutic activity of pyrazole derivatives against HIV that will be helpful for designing pyrazole containing compounds for anti-HIV activity.

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

Therapeutic potential of indole derivatives as anti-HIV agents: A mini-review

2021 ◽  
Vol 21 ◽  
Author(s):  
Qingtai Chen ◽  
Chongchong Wu ◽  
Jinjin Zhu ◽  
Enzhong Li ◽  
Zhi Xu
Keyword(s):  
Therapeutic Potential ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Bioactive Molecules ◽  
Indole Derivatives ◽  
Chemical Structures ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

: Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs over different disease progress has made AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, together with the severe side effects of anti-HIV agents, compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for the design and development of novel drugs. Indole derivatives are potential inhibitors of HIV enzymes such as reverse transcriptase, integrase and protease, and some indole-based agents like Delavirdine have already been applied in clinics or under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement of indole derivatives including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship and mechanisms of action are also discussed.

Synthesis and anti-HIV Activity of a Series of 2-Indolinones and Related Analogues

1993 ◽  
Vol 4 (1) ◽  
pp. 27-39 ◽  
Author(s):  
J. M. Smallheer ◽  
M. J. Otto ◽  
C. A. Amaral-Ly ◽  
R. A. Earl ◽  
M. J. Myers ◽  
...  
Keyword(s):  
Cell Protection ◽  
Structure Activity ◽  
Virus Activity ◽  
Immunodeficiency Virus ◽  
Dependent Cell ◽  
Syncytia Formation ◽  
Anti Hiv Agents ◽  
Related Compounds ◽  
Anti Hiv

A novel series of 2-indolinones with in vitro anti-HIV (human immunodeficiency virus) activity is described. Two structurally related compounds, 1, 3,3-(4- N-methyl-1,2,5,6-tetrahydropyridylmethyl)-1- phenyl-2-indolinone, and 2, its 4- N-methylpiperidinylmethyl analogue (Fig. 1), formed the basis of a structure-activity study. The synthesis of approximately 50 analogues and their respective activities vs. HIV are presented. Both 1 and 2 were effective inhibitors of HIV(IIIb) in cell protection assays with IC90 values of 4.4 and 14.9μM (2.2 and 7.9μg ml−1), respectively. In the same concentration range, 1 and 2 also inhibit syncytia formation. These compounds represent a novel class of anti-HIV agents which appear to act by inhibiting virus-dependent cell fusion.

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

Design, Synthesis, Molecular Modeling and Anti-HIV Assay of Novel Quinazolinone Incorporated Coumarin Derivatives

2020 ◽  
Vol 18 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Mahdieh Safakish ◽  
Zahra Hajimahdi ◽  
Mohammad R. Aghasadeghi ◽  
Rouhollah Vahabpour ◽  
Afshin Zarghi
Keyword(s):  
Therapeutic Index ◽  
In Vivo Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Phenyl Derivative ◽  
Hiv Therapy ◽  
Anti Hiv Agents ◽  
Anti Hiv

Background: The emergence of drug-resistant viral strains has created the need for the development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV lifecycle. Objective: Considering the pharmacophore of integrase inhibitors, one of the validated targets for anti-HIV therapy, we designed a quinazolinone incorporated coumarin scaffold to affect HIV. Method: Coumarin is a beta enol ester and also a well-known drug scaffold. Designed structures were prepared using a one-pot three-compo Results: In vitro anti-HIV and cytotoxicity assay indicated that more than half of the compounds had EC50 values lower than 50 µM. Unsubstituted phenyl derivative showed the highest activity and selectivity with an EC50 value of 5 µM and a therapeutic index of 7. Compounds were docked into the integrase active site to investigate the probable mechanism of action. Accordingly, the hydroxyl moiety of coumarin along with the carbonyl of the quinazolinone ring could function as the metal chelating group. Quinazolinone and phenyl groups interact with side chains of IN residues, as well. Conclusion: Here, a novel anti-HIV scaffold is represented for further modification and in-vivo studies.

scholarly journals Effect upon the anti-HIV Activity of 3′-Azido-3′-Deoxythymidine and 3′-Fluoro-3′-Deoxythymidine of Combination with anti-Herpes Nucleoside Analogues

1993 ◽  
Vol 4 (1) ◽  
pp. 41-47 ◽  
Author(s):  
S. Cox ◽  
A. Vissgården ◽  
B. Wahren
Keyword(s):  
Aids Patients ◽  
Hiv Therapy ◽  
Immunodeficiency Virus ◽  
Life Threatening ◽  
The Individual ◽  
Lower Ratio ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Antagonistic Interactions

The treatment of the severe and often life-threatening herpesvirus infections which commonly occur in AIDS patients is complicated by the need to treat simultaneously with drugs directed against the human immunodeficiency virus (HIV). Combining together different drugs in this way can lead to effects upon the activities of the individual drugs, such as synergism or antagonism. The effect upon the anti-HIV activity of 3′-azido-3′-deoxythymidine (AZT) and 3′-fluoro-3′-deoxythymidine (FLT) of combination with the anti-herpesvirus drugs 9-(1,3-dihydroxy-2-propoxymethyl-)guanine (DHPG; ganciclovir) and (-)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine ([-]-2HM-HBG) was investigated. Neither DHPG nor (-)-2HM-HBG showed antiviral activity against HIV-1 up to 50 [AM. When combined with AZT or FLT at ratios of antiherpes:anti-HIV drug of 10:1 or greater, both DHPG and (-)-2HM-HBG antagonized the anti-HIV activity of AZT and FLT. When combined at a lower ratio (1:1), there was no effect upon the anti-HIV activity of either AZT or FLT. The phosphorylation of FLT was found to be unchanged in the presence of DHPG or (-)-2HM-HBG, indicating that the mechanism of the antagonism was not owing to an effect of DHPG or (-)-2HM-HBG upon the metabolism of the anti-HIV drugs. The results suggest that combination chemotherapy with the anti-herpes drugs DHPG/(-)-2HM-HBG and AZT/FLT should be used cautiously. The possibility of such antagonistic interactions should be borne in mind when considering the choice of drug and ratio for treatment of herpesvirus infections in AIDS patients on anti-HIV therapy.

New Advances in the Pharmacological Treatment of Human Immunodeficiency Virus (HIV) Infection: Focus on Protease Inhibitors

1997 ◽  
Vol 10 (1) ◽  
pp. 20-51 ◽  
Author(s):  
Catherine M. Oliphant ◽  
Scott M. Bonnema
Keyword(s):  
Hiv Infection ◽  
Protease Inhibitors ◽  
Factors Affecting ◽  
Hiv Therapy ◽  
New Class ◽  
Complete Knowledge ◽  
Immunodeficiency Virus ◽  
Infection Focus ◽  
Anti Hiv Agents ◽  
Anti Hiv

The introduction of a new class of anti-HIV agents, the protease inhibitors, has given new hope to patients with HIV infection. Use of these agents requires the pharmacist to have a complete knowledge of phar macokinetics, adverse reactions, drug-drug interactions, and resistance profiles. Patient compliance is one of the most important factors affecting the success and failure of protease inhibitor therapy. Pharma cists have the opportunity to positively influence outcomes of HIV therapy.

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