Anti HIV Research Articles

Anti-diabetic, Anti-cancer Potential and Anti HIV of Bitter Gourd (Momordica charantia) Extract: A Mini Review

Aims: To review the antidiabetic properties, pharmacological characteristics, and phytochemical research on Momordica Ccharantia (bitter gourd) and assess its potential as a therapeutic agent for diabetes and cancer prevention. Study Design: Review of existing literature and research studies, including pre-clinical trials and animal and in vitro studies. Methodology: Analysis of traditional uses, pharmacological data, and phytochemical research on M. Charantia. Evaluation of anti-diabetic and anti-HIV properties based on available studies. Results: Charantia has shown anti-diabetic and hypoglycemic effects in pre-clinical studies. Limited and unreliable clinical data due to poor research design and inadequate statistical power. Recent studies indicate potential anti-tumor, anti-diabetic, and anti-HIV properties. Plant extract components have demonstrated effectiveness in cancer prevention through immune function enhancement, induction of cell death, and inhibition of cancer-related processes. Conclusion: M. Charantia holds promise as a therapeutic agent for diabetes management and cancer prevention. However, there is a need for better-designed clinical trials to confirm its efficacy and establish reliable clinical evidence.

Comparison of feline and human immunodeficiency virus reverse transcriptase enzymes through chemical screening and computational analysis.

Feline immunodeficiency virus (FIV) is a common infection found in domesticated and wild cats worldwide. Despite the wealth of therapeutic understanding of the disease in humans, considerably less information exists regarding the treatment of the disease in felines. Current treatment relies on drugs developed for the related human immunodeficiency virus (HIV) and includes compounds of the popular non-nucleotide reverse transcriptase (NNRTI) class. This is despite FIV-RT being only 67% similar to HIV-1 RT at the enzyme level, increasing to 88% for the allosteric pocket targeted by NNRTIs. The goal of this project was to try to quantify how well the more extensive pharmacological knowledge available for human disease translates to felines. To this end we screened known NNRTIs and 10 diverse pyrimidine analogs identified virtually. We use this chemo-centric probe approach to (a) assess the similarity between the two related RT targets based on the observed experimental inhibition values, (b) try to identify more potent inhibitors at FIV, and (c) gain a better appreciation of the structure-activity relationships (SAR). We found the correlation between IC50s at the two targets to be strong (r2 = 0.87) and identified compound 1 as the most potent inhibitor of FIV with IC50 of 0.030 μM ± 0.009. This compared to FIV IC50 values of 0.22 ± 0.17 μM, 0.040 ± 0.010 μM and >160 μM for known anti HIV-1 RT drugs Efavirenz, Rilpivirine, and Nevirapine, respectively. This knowledge, along with an understanding of the structural origin that give rise to any differences could improve the way HIV drugs are repurposed for FIV.

Tinospora cordifolia as medicinal herb

Tinospora cordifolia is a popular medicinal plant which is used in several traditional drugs to cure several conditions. The common names are Amrita and Guduchi and belong to family Menispermaceae.. It is considered an essential herbal plant of Indian system of drug(ISM) and has been used in the treatment of fever, urinary problem, dysentery, skin conditions leprosy, diabetes, and numerous further conditions. The plant reported containing chemical constituents including Alkaloids, Terpenoids, Lignans, Steroids and others that establish the photochemistry and pharmacological exertion of Tinospora cordifolia. The present review highlights the pharma ecological significance viz antioxidant exertion, antimicrobial exertion, antibacterial exertion, antifungal exertion, anti-diabetic exertion, antistress exertion, hypolipidaemic effect, hepatic complaint, anticancer anti HIV eventuality, antiosteoporotic goods, antitoxic goods, crack mending, anticomplementary exertion, and immunomodulation exertion, systemic infection and Parkinson’s complaint.

Design and sustainable synthesis of small mannose-based glycodendrons as ligands for HIV-1 envelope protein gp120: Toward an explanation for their binding

On the basis of the interesting properties that glucuronic acid-based glycodendrimers and glycodendrons show against Dengue virus through their interaction with its envelope protein, herein we describe the design, sustainable synthesis and anti HIV-1 evaluation of a series of mannose-based glycodendrimers bearing different scaffolds, valency and functional groups at the focal position. Their sustainable chemical synthesis was performed using microwave-assisted copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction to yield glycoconjugates with full conversions (99%), allowing the reduction of the reaction time from 16 h to 60–120 min. Surface plasmon resonance studies have demonstrated that the small mannose-based glycodendrons (divalent derivatives) give the best binding interactions with the HIV-1 gp120 envelope protein, being the most active those that have a methoxymethyl group or an azidomethyl group at the focal position. Molecular modeling studies were carried out to simulate and explain the binding observed by surface plasmon resonance. This work reports a sustainable synthesis of small mannose-based glycodendrons as novel and potent anti HIV lead compounds.

Ethno-Botanical and Phytopharmacological Study of Limnophila rugosa Roth. Merr. (Scrophulariaceae): Mini Review

Background: Limnophila rugosa (Scrophulariaceae) is an aquatic and perennial herb finds its natural habitats in ponds, rivers, lakes as well as marshy lands of India. The traditional practitioners of Bolangir and Bargarh District of Odisha use this plant as a source of Bhringaraj. Therapeutically, it is used as diuretic, stomachic, digestive tonic and as a hair perfume, treatment of elephantiasis, diarrhoea, dysentery, dyspepsia and urinary burning. Objective: The present study was focused to provide the information regarding its traditional uses, compounds identified from different parts and essential oil; and the pharmacological activities of the reported compounds, which will bring the scope for future research. Methods: Extensive literature survey was carried out up to 2021 in Google scholar, Web of science, scopus, pub med, science direct, springer, Taylor and Francis using key words pharmacognostical, phytochemical and pharmacological aspect of L. rugosa. Result: The study revealed diverse chemical compounds; flavonoids, terpenoids, amino acids, alcohol, phenol, aldehyde, ketone, carboxylic acid and ether. 5,7-Dihydroxy-6,8,4'-trimethoxyflavone (Nevadensin), 5-Hydroxy-6,7,4'-trimethoxyflavone (Salvigenin), Betulin, betulinic acid, caryophyllene, cis-anethole, methylchavicol were found as major compounds. Pharmacological activities such as antimicrobial, anti-inflammatory, diuretic and hypotensive was reported. The identified compounds exhibited several pharmacological activities including antibacterial, antimicrobial, antifungal, anxiolytic, anti-inflammatory, analgesic, antioxidant, anti-tubercular, anti-tumour, anti-cancer, immunomodulatory, hepatoprotective, antiulcer, antidiabetic, antinociceptive, antimalarial, antiviral, anti-hyperlipidaemic, anti HIV, insecticidal, herbicidal, antifeedant, anti-coagulant, gastro-protective, antihelmintic. Conclusion: As, most of the compounds exhibited significant antimicrobial, antibacterial and antifungal activity so; a novel dosage form can be prepared from the essential oil of L. rugosa for antimicrobial activity.

IL-15 enhances HIV-1 infection by promoting survival and proliferation of CCR5+CD4+ T cells.

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, and facilitated HIV-1 infection in vitro and in humanized mice. Our study suggests that IL-15 plays confounding roles in HIV-1 infection, and future studies on the IL-15-based boosting of anti-HIV-1 immunity should carefully examine the potential effects on the expansion of HIV-1 reservoirs in CCR5+CD4+ T cells.

Synthesis, X-ray structure, DFT investigation, and molecular docking of 1,3,5-tricyclohexyl-1,3,5-triazinane-2,4,6-trione, a cyclic polyamide with anti HIV-1 (RT), antiplatelet, and anticoagulant activities

Synthesis, X-ray structure, DFT investigation, and molecular docking of 1,3,5-tricyclohexyl-1,3,5-triazinane-2,4,6-trione, a cyclic polyamide with anti HIV-1 (RT), antiplatelet, and anticoagulant activities

CD4 binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wild-type animals.

Passive transfer of broadly neutralizing anti-HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4 binding site (CD4bs) on HIV-1 Env are among the most broadly active, but to date, responses elicited against this epitope in vaccinated animals have lacked potency and breadth. We hypothesized that CD4bs bNAbs resembling the antibody IOMA might be easier to elicit than other CD4bs antibodies that exhibit higher somatic mutation rates, a difficult-to-achieve mechanism to accommodate Env's N276gp120 N-glycan, and rare five-residue light chain complementarity-determining region 3.As an initial test of this idea, we developed IOMA germline-targeting Env immunogens and evaluated a sequential immunization regimen in transgenic mice expressing germline-reverted IOMA. These mice developed CD4bs epitope-specific responses with heterologous neutralization, and cloned antibodies overcame neutralization roadblocks, including accommodating the N276gp120 glycan, with some neutralizing selected HIV-1 strains more potently than IOMA. The immunization regimen also elicited CD4bs-specific responses in mice containing polyclonal antibody repertoires as well as rabbits and rhesus macaques. Thus, germline targeting of IOMA-class antibody precursors represents a potential vaccine strategy to induce CD4bs bNAbs.

LOW COST PRODUCTION OF SPIRULINA (Spirulina platensis) THROUGH TREATMENT OF WASTEWATER

Spirulina is multi cellular, autotrophic and filamentous blue-green microalgae possessed rich protein, vitamins, minerals and pigments. It showed various pharmaceutical activities including anticancer and anti HIV activities. It also used as animal feed for rich protein content. Black water refers to toilet water which turned and one of the most significant sources of human pathogens and source of ground water pollution. In the present study focused to treat the wastewater through the cultivation of S. platensis. Culturemedium was divided into three groups (Group I (100% black water), Group II (50% black water), Group III (25% black water) and Group IV (Chemical medium). Water quality parameters were measure before and after cultivation of spirulina. A healthy and high amount of S. platensis was cultured in group III (25% black water) more or less similar to the chemical medium. The cost effect ratio for the synthetic medium showed the high expenses. On the other hand, in wastewater culture spirulina showed a maximum gain from zero cost management or without loss of cost. With regard to waste water treatment, the culturing of spirulina favorably altered the physical and chemical parameters of the wastewater except chlorides, total hardness and total alkalinity.The present study indicates that spirulina canbe successfully cultured in black wastewater with expected yield. Furthermore the cultured water can also be used for irrigation purpose with 25% addition of freshwater or as such. Since there is no bad odour and other toxic material it can also be used for toilet flush.

Autophagy inducer rapamycin treatment reduces IFN-I-mediated Inflammation and improves anti-HIV-1 T cell response in vivo.

A hallmark of HIV-1 infection is chronic inflammation, even in patients treated with antiretroviral therapy (ART). Chronic inflammation drives HIV-1 pathogenesis, leading to loss of CD4+ T cells and exhaustion of antiviral immunity. Therefore, strategies to safely reduce systematic inflammation are needed to halt disease progression and restore defective immune responses. Autophagy is a cellular mechanism for disposal of damaged organelles and elimination of intracellular pathogens. Autophagy is pivotal for energy homeostasis and plays critical roles in regulating immunity. However, how it regulates inflammation and antiviral T cell responses during HIV infection is unclear. Here, we demonstrate that autophagy is directly linked to IFN-I signaling, which is a key driver of immune activation and T cell exhaustion during chronic HIV infection. Impairment of autophagy leads to spontaneous IFN-I signaling, and autophagy induction reduces IFN-I signaling in monocytic cells. Importantly, in HIV-1-infected humanized mice, autophagy inducer rapamycin treatment significantly reduced persistent IFN-I-mediated inflammation and improved antiviral T cell responses. Cotreatment of rapamycin with ART led to significantly reduced viral rebound after ART withdrawal. Taken together, our data suggest that therapeutically targeting autophagy is a promising approach to treat persistent inflammation and improve immune control of HIV replication.

Formulation and Characterization of Tenofovir Disproxyl Fumerate Nanoparticles prepared by Nanoprecipitation Method

Tenofovir disproxyl fumerate (TDF) is widely used drug in anti HIV treatment. The main disadvantage with TDF is its low bioavailability. To overcome this problem TDF is formulated in to nanoparticles by using nanoprecipitation method. The formulated nanoparticles were in the range of 106.8nm to 516.4nm. The effect of PLGA and TPGS on the formulated nanoparticles were also studied. It is evident that the concentration of PLGA played an important role in the entrapment and drug loading capacity. On the basis of drug loaded and entrapment efficiency the F8 formulation was considered as optimized formulation. Different analytical techniques were used to determine the amount of drug present in the optimized formulation. The optimized formulation (F8) was subjected to different drug release kinetic models and its stability studies were also conducted in accordance with ICH guidelines.

RP-HPLC stability method development & validation for anti-HIV drugs cabotegravir & rilpivirine in I.M. injection and in human plasma

In Pharmaceutical & Medical Health Sciences there are necessities for development of analysis methods for medicines in various dosage forms. Currently the use of RP-HPLC is primarily applied for testing of medicines in various dosage forms, and to study bio analysis in human plasma matrix. The present method is developed for analysis of anti HIV drugs cabotegravir CAB and rilpivirine RILP in pure api & Intramuscular Injection dosage forms, and also in human plasma. The HPLC method is optimized for analysis of these two drugs in combined forms for swift analysis with very less amount of drugs utilized for testing purposes. The concentration range used for the linearity studies is 2.5 to 15µg/ml for CAB cabotegravir & for Rilpivirine RILP it is 3.75 to 22.5µg/ml. Wavelength selected for estimation is 242.5nm and column used was Kinetex C-18 column (250mm x 4.6mm, 5 µm id). The Retention-time obtained were 2.14min for CAB & 3.12min for RILP. The R2 was found to be 0.999 for both drugs. The method is applied for analysis of drugs in i.m. injections, individually & in combined forms.

Blood donors

Evaluation of TTI (transfusion transmitted infections) are essential for assessing the safety of blood supply and monitoring the efficacy of currently employed screening procedures. Objective: To assess the prevalence of HBV, HCV and HIV among replacement donors and voluntary donor in association with the Kuppuswamy’s socioeconomic status. Material and Methods: A retrospective analysis of total 10569 blood donors from Jan2014 to Sep 2015 was conducted at a blood bank in a tertiary care hospital in North India, Teerthanker Mahaveer Medcial college and research centre. Donor with hemoglobin (Hb) less than 12.5gm% or known seropositive for TTI were deferred and excluded from the study group. The hemoglobin level was measured by copper sulphate method, samples were screened for: a) HIV-1 and p antigen ELISA kits from Mitra& Co. ltd , for anti HIV I and II 4th generation Microlisa- HIV Ag and Ab. b) HBsAg- Hepalisac) anti HCV d) Malaria Age) Syphilis. Observation: The prevalence of HBV and HCV was noted to be higher among replacement donors as compared to voluntary donors, while in HIV, the prevalence was noted only in voluntary donors. Total 10,569 blood donors were grouped as per the KSESS, maximum donors in lower middle class III-5789.

Synthesis, characterization and anti HIV1 screening of some novel clubbed benzimidazole derivatives

A humble and a competent technique was improved in production of novel substituted benzimidazole derivatives by the condensation of various diamines with 2-amino-benzoic acid and many substituted benzoyl chloride reactions have demonstrated the benefits of classical reactions; convenient operation, and good yields. Finally, it has treated with phosphorous pentachloride and sodiumazide reaction to yield benzimidazole clubbed with tetrazole moiety compounds which were established by an Elemental analysis, IR, 1H NMR, 13C NMR and Mass spectra and screening of various biological studies also recorded.

Significance of Adopting Nucleic Acid Amplification Technique for Blood Donor Screening in a Resource Limited Setting: A Study from a Single Centre in South India.

Nucleic acid Amplification testing (NAT) has helped improve blood safety and detect window period and Occult Hepatitis B infections (OBI) This study was aimed at determining the following in blood donors: 1. seroprevalence of HIV, HBV & HCV, malarial parasite and Syphlis 2. NATand seroyield for HIV, HBV and HCV 3. viral load in NAT yield donations 4. Pattern of HBV serological markers in HBV NAT yield donations 80,809 blood donations were screened over an 8 year period (2012-2019) for antiHIV I and II, HBsAg, antiHCV antibodies, malarial parasite and VDRL. Seronegative samples were tested by NAT using a multiplex PCR in a pool of six. NAT yield samples were tested for viral load and HBV serological markers. Seropositive samples were tested for NAT and checked for seroyield. SPSS windows version 24.0 was used for statistical analysis. 1.07% of blood donors were found to be seropositive with 0.08%, 0.86%, 0.09%, 0.03% and 0 for anti HIV I and II, HBsAg, antiHCV, VDRL and Malarial parasite respectively. Out of 79,938 seronegative samples, 20 samples (0.025%) were NAT positive for Hepatitis B with a NAT yield OF 1:3997. Out of the 20 NAT positive samples, 17 were OBI and three were window period infections. 14 NAT yield samples subjected to a HBV viral load assay showed a range of < 6-146IU/ml. Minipool NAT in pools of six is able to indentify both OBI and window period infections. NAT could significantly improve the blood safety in a resource limited setting like India.

ACUTE 8 AND CHRONIC TOXICOLOGICAL STUDIES OF THE BIOSYNTHESIZED GOLD NANOPARTICLES ON WISTAR RATS

In the present study, gold nanoparticles were biosynthesized using green extracts of medicinal plants. The synthesized nanoparticles were screened for in vitro anti HIV, anticancer and anti-tuberculosis activity. All the three studies demonstrated potential agonistic effects of the synthesized gold nanoparticles against HIV, cervical cancer and tuberculosis. Simultaneously, the in vitro cytotoxicity was checked in epithelial cell lineage such as Vero cell line. The results of in vitro cytotoxicity showed that the synthesized nanoparticles were non-toxic to the normal cells. The results of the in vivo toxicity will help in the effective formulation of the gold nanoparticles towards drug development for HIV, cervical cancer and tuberculosis. The results of acute toxicity and chronic toxicity implied that the animals did not suffer from any adverse effects following administration of gold nanoparticles. The animals survived both single dose and consecutive dosage for 28 days. The animals were observed to be normal without any abnormal behavioral changes. The blood parameters showed no significant difference between the control and treated animals on various parameters under consideration. Hematology reports suggested that the metabolic parameters of the treated group do not vary significantly with the control group. All the hematology reports implied that the biosynthesized gold nanocompounds did not elicit adverse effects on the animal model system. In the histopathology investigation, the major organs, such asthe brain, the heart, the kidney, the liver and the spleen were excised from the control and treated animals. The tissue samples were sectioned, stained with eosin red and viewed under microscope. The microscopic examination of all the tissues represented normal cellular organization without any distinctive tissue degeneration and organ damage. The present study has been successfully carried out to check the in vivo toxicological effects of the biosynthesized gold nanocompounds adapting Wistar rats as animal model system. The outcome of the study emphasized that the biosynthesized AuNPs were non-toxic to the treated animal model system. Further the study will focus on other toxicological implications such as immunotoxicity, neurotoxicity, reproductive toxicity and genotoxicity. The biosynthesized gold nanocompounds have a promising role as versatile nanomaterials towards multiple applications.

Seroprevalence of HBsAg, Anti-HBs, Anti-HCV and Anti-HIV in Behçet’s Disease

Introduction: Behçet's disease defined by Turkish dermatologist Hulusi Behçet is an inflammatory disease of unknown etiology and characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis and skin lesions. We aimed to evaluate hepatitis B virus, hepatitis C virus and human immunodeficiency virus seroprevalence in Behçet's Disease.&#x0D; Material and Method: Patients diagnosed with Behçet’s diseaseand followed up by the dermatology outpatient clinic during 12-years period between July 2008 and July 2020 were retrospectively analyzed. Demographic datas and HBsAg, anti-HBs, anti-HCV, Anti-HIV results of the patients were recorded.&#x0D; Results: 359 patients with Behçet’s disease were been evaluated in this study. Of these patients, 189 (52.6%) were female, 170 (47.4%) were male and the mean age was 37.7±12.3 years. HBsAg was positive in 6 (1.6%) patients and Anti-Hbs ab in 82 (7.7%) patients. Anti HIV ab was negative in all patients. Anti-HCV antibodies were found positive in only one case (0.2%), and this was confirmed by testing for hepatitis C virus-ribonucleic acid (HCV RNA). HCV RNA was negative in this patient. &#x0D; Conclusion: When compared with the general population, seropositivity rates were not detected to be high in Behçet's patients. In fact, the immunity rates were found very low. Based on such a finding, it was concluded that screening is required due to increasing immunosupressive treatments today, and individuals should be vaccinated in cases where HBV indicators are negative.In the other studies, investigating the entity, seropositivity rates have been found similar to those in the population. Considering that serological data show regional differences, we thought that, our study will contribute to the literature both national and international grades due to large patient population in our region.

Bioprospecting of insect nest associated actinobacteria with special reference to antimicrobial and anti HIV activity

The present study attempted to explore actinobacteria from different insect nest samples for antimicrobial activity. Totally, 43 actinobacterial colonies were recovered from ant nest, termite nest, wasp nest and blanket worm nest samples by adopting standard spread plate method. Screening of antimicrobial properties of actinobacterial strains was determined by agar plug method. Two actinobacterial strains AN1 and AN5 showed promising activity (14-18 mm inhibition) against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, carbapenem resistant Klebsiella pneumoniae and Mycobacterium smegmatis. Both the strains produced antimicrobial compound earlier on ISP2 agar when compared to ISP2 broth. Crude extracts from the strains AN1 and AN5 were produced by adopting agar surface fermentation and extracted using ethyl acetate. Based on the studied phenotypic characteristics, actinobacterial strains AN1 and AN5 isolated from ant nest were identified as Streptomyces sp. In addition to antimicrobial activity, extracts also showed anti-HIV activity. This study concluded that insect nest is a promising source for bioactive actinobacteria. Two potential Streptomyces sp. AN1 and AN5 isolated from ant nest will be promising sources for antimicrobial metabolites against drug resistant bacteria, retrovirus and mycobacterial pathogens.

Screening of anti-HIV activities in ethanol extract and fractions from Ficus fistulosa leaves.

Human immunodeficiency virus (HIV) infection is considered as a major immunosuppressive disease linked to malignancies and other opportunistic infections. Recently, the high prevalence of HIV drug-resistant strains required a high demand for novel antiviral drug development, especially in herbal medicine approaches. The objective of this study was to evaluate the possibility of Ficus fistulosa leaves can inhibit HIV replication in ethanol extract form as well as its fractions using chloroform, ethyl acetate, and butanol solvents. F.fistulosa leaves were extracted using ethanol as a solvent and further gradually fractionated in chloroform, ethyl acetate, and butanol solvents. The targeted persistently infected virus (MT4/HIV) cell lines were cocultured with ethanol extract and fractions at different time points. The syncytium formation and cytotoxicity assays were performed to evaluate the potential antiviral activity of F.fistulosa leaves. One of the four tested extract/fractions showedantiviral activity against HIV. The ethanol extractshowed weak inhibition with a high level of toxicity (IC50=8.96μg/mL, CC50≥50μg/mL, and SI=5.58). Meanwhile, chloroform fraction effectively inhibited the MT4/HIV cell proliferation while keeping the toxicity to a minimal level (IC50=3.27μg/mL, CC50=29.30μg/mL, and SI=8.96). In contrast of ethyl acetate fraction and butanol fraction showed no anti HIV activity with a high level of toxicity (CC50≥50μg/mL) and low SI value (>2.17μg/mL and >0.97μg/mL). Chloroform fraction of F.fistulosa leaves showed effectively as anti-viral activity against MT4/HIV cells.

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

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.