scholarly journals AntiHIV-Pred: web-resource for in silico prediction of anti-HIV/AIDS activity

2019 ◽  
Vol 36 (3) ◽  
pp. 978-979 ◽  
Author(s):  
Leonid Stolbov ◽  
Dmitry Druzhilovskiy ◽  
Anastasia Rudik ◽  
Dmitry Filimonov ◽  
Vladimir Poroikov ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Biological Activities ◽  
Supplementary Information ◽  
Careful Examination ◽  
Web Resource ◽  
Validation Procedure ◽  
Structural Formulae ◽  
Anti Hiv ◽  
Positive Results ◽  
Hiv 1

Abstract Motivation Identification of new molecules promising for treatment of HIV-infection and HIV-associated disorders remains an important task in order to provide safer and more effective therapies. Utilization of prior knowledge by application of computer-aided drug discovery approaches reduces time and financial expenses and increases the chances of positive results in anti-HIV R&D. To provide the scientific community with a tool that allows estimating of potential agents for treatment of HIV-infection and its comorbidities, we have created a freely-available web-resource for prediction of relevant biological activities based on the structural formulae of drug-like molecules. Results Over 50 000 experimental records for anti-retroviral agents from ChEMBL database were extracted for creating the training sets. After careful examination, about seven thousand molecules inhibiting five HIV-1 proteins were used to develop regression and classification models with the GUSAR software. The average values of R2 = 0.95 and Q2 = 0.72 in validation procedure demonstrated the reasonable accuracy and predictivity of the obtained (Q)SAR models. Prediction of 81 biological activities associated with the treatment of HIV-associated comorbidities with 92% mean accuracy was realized using the PASS program. Availability and implementation Freely available on the web at http://www.way2drug.com/hiv/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia

2002 ◽  
Vol 128 (2) ◽  
pp. 221-228 ◽  
Author(s):  
R. E. J. H. SENTJENS ◽  
Y. SISAY ◽  
H. VRIELINK ◽  
D. KEBEDE ◽  
H. J. ADÈR ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Sexual Behaviour ◽  
Blood Donors ◽  
Transmitted Disease ◽  
Urban Residents ◽  
Sexual Transmitted Disease ◽  
Low Prevalence ◽  
Anti Hiv ◽  
Hiv 1

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5·9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10·5%) were HIV-1 infected, and 1/797 (0·1%) was HIV-2 infected. 1/240 (0·4%) individuals from the rural population were HIV-1 infected. 198/480 (41·3%) female attendees, and 106/419 (25·3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0·2%) male, and 2 (0·4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0·4% among urban residents to 25·3–41·3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.

Highly Potent and Orally Active CCR5 Antagonists as Anti-HIV-1 Agents:  Synthesis and Biological Activities of 1-Benzazocine Derivatives Containing a Sulfoxide Moiety

2006 ◽  
Vol 49 (6) ◽  
pp. 2037-2048 ◽  
Author(s):  
Masaki Seto ◽  
Katsuji Aikawa ◽  
Naoki Miyamoto ◽  
Yoshio Aramaki ◽  
Naoyuki Kanzaki ◽  
...  
Keyword(s):  
Biological Activities ◽  
Ccr5 Antagonists ◽  
Orally Active ◽  
Anti Hiv ◽  
Hiv 1

Orally active CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological activities of 1-benzazepine derivatives containing a sulfoxide moiety

2005 ◽  
Vol 13 (2) ◽  
pp. 363-386 ◽  
Author(s):  
Masaki Seto ◽  
Naoki Miyamoto ◽  
Katsuji Aikawa ◽  
Yoshio Aramaki ◽  
Naoyuki Kanzaki ◽  
...  
Keyword(s):  
Biological Activities ◽  
Ccr5 Antagonists ◽  
Orally Active ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Orally Active CCR5 Antagonists as Anti-HIV-1 Agents 2: Synthesis and Biological Activities of Anilide Derivatives Containing a Pyridine N-Oxide Moiety

2004 ◽  
Vol 52 (7) ◽  
pp. 818-829 ◽  
Author(s):  
Masaki Seto ◽  
Yoshio Aramaki ◽  
Hiroshi Imoto ◽  
Katsuji Aikawa ◽  
Tsuneo Oda ◽  
...  
Keyword(s):  
Biological Activities ◽  
Ccr5 Antagonists ◽  
Orally Active ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals (Q)SAR Models of HIV-1 Protein Inhibition by Drug-Like Compounds

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 87 ◽  
Author(s):  
Leonid A. Stolbov ◽  
Dmitry S. Druzhilovskiy ◽  
Dmitry A. Filimonov ◽  
Marc C. Nicklaus ◽  
Vladimir V. Poroikov
Keyword(s):  
Hiv Treatment ◽  
Reverse Transcriptase Inhibitors ◽  
Protein Inhibition ◽  
Web Resource ◽  
Structure Activity ◽  
Resistant Strains ◽  
Sar Analysis ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Chemical Class

Despite the achievements of antiretroviral therapy, discovery of new anti-HIV medicines remains an essential task because the existing drugs do not provide a complete cure for the infected patients, exhibit severe adverse effects, and lead to the appearance of resistant strains. To predict the interaction of drug-like compounds with multiple targets for HIV treatment, ligand-based drug design approach is widely applied. In this study, we evaluated the possibilities and limitations of (Q)SAR analysis aimed at the discovery of novel antiretroviral agents inhibiting the vital HIV enzymes. Local (Q)SAR models are based on the analysis of structure–activity relationships for molecules from the same chemical class, which significantly restrict their applicability domain. In contrast, global (Q)SAR models exploit data from heterogeneous sets of drug-like compounds, which allows their application to databases containing diverse structures. We compared the information for HIV-1 integrase, protease and reverse transcriptase inhibitors available in the EBI ChEMBL, NIAID HIV/OI/TB Therapeutics, and Clarivate Analytics Integrity databases as the sources for (Q)SAR training sets. Using the PASS and GUSAR software, we developed and validated a variety of (Q)SAR models, which can be further used for virtual screening of new antiretrovirals in the SAVI library. The developed models are implemented in the freely available web resource AntiHIV-Pred.

Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities

2016 ◽  
Vol 25 (9) ◽  
pp. 1861-1876 ◽  
Author(s):  
Z. Hajimahdi ◽  
R. Zabihollahi ◽  
M. R. Aghasadeghi ◽  
S. Hosseini Ashtiani ◽  
A. Zarghi
Keyword(s):  
Carboxylic Acid ◽  
Biological Activities ◽  
Design Synthesis ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Inhibition of In Vivo HIV Infection in Humanized Mice by Gene Therapy of Human Hematopoietic Stem Cells with a Lentiviral Vector Encoding a Broadly Neutralizing Anti-HIV Antibody

2010 ◽  
Vol 84 (13) ◽  
pp. 6645-6653 ◽  
Author(s):  
Aviva Joseph ◽  
Jian Hua Zheng ◽  
Ken Chen ◽  
Monica Dutta ◽  
Cindy Chen ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Lentiviral Vector ◽  
High Titer ◽  
Hematopoietic Stem ◽  
Specific Antibodies ◽  
Human B Cells ◽  
Fold Reduction ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Due to the inherent immune evasion properties of the HIV envelope, broadly neutralizing HIV-specific antibodies capable of suppressing HIV infection are rarely produced by infected individuals. We examined the feasibility of utilizing genetic engineering to circumvent the restricted capacity of individuals to endogenously produce broadly neutralizing HIV-specific antibodies. We constructed a single lentiviral vector that encoded the heavy and light chains of 2G12, a broadly neutralizing anti-HIV human antibody, and that efficiently transduced and directed primary human B cells to secrete 2G12. To evaluate the capacity of this approach to provide protection from in vivo HIV infection, we used the humanized NOD/SCID/γc null mouse model, which becomes populated with human B cells, T cells, and macrophages after transplantation with human hematopoietic stem cells (hu-HSC) and develops in vivo infection after inoculation with HIV. The plasma of the irradiated NOD/SCID/γc null mice transplanted with hu-HSC transduced with the 2G12-encoding lentivirus contained 2G12 antibody, likely secreted by progeny human lymphoid and/or myeloid cells. After intraperitoneal inoculation with high-titer HIV-1JR-CSF, mice engrafted with 2G12-transduced hu-HSC displayed marked inhibition of in vivo HIV infection as manifested by a profound 70-fold reduction in plasma HIV RNA levels and an almost 200-fold reduction in HIV-infected human cell numbers in mouse spleens, compared to control hu-HSC-transplanted NOD/SCID/γc null mice inoculated with equivalent high-titer HIV-1JR-CSF. These results support the potential efficacy of this new gene therapy approach of using lentiviral vectors encoding a mixture of broadly neutralizing HIV antibodies for the treatment of HIV infection, particularly infection with multiple-drug-resistant isolates.

scholarly journals Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2451
Author(s):  
Ivana Křížová ◽  
Alžběta Dostálková ◽  
Edison Castro ◽  
Jan Prchal ◽  
Romana Hadravová ◽  
...  
Keyword(s):  
Reverse Transcription ◽  
Biological Activities ◽  
Reverse Transcriptase Activity ◽  
Genomic Rna ◽  
Rna Packaging ◽  
Fullerene Derivatives ◽  
Viral Genomic Rna ◽  
Anti Hiv ◽  
Hiv 1

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives’ action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C70 derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C70 derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription—without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives’ oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.

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