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The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

Introduction: The human immunodeficiency virus type 1 (HIV-1) is the agent that produces AIDS, a disease recognized for more than forty years, which has reached pandemic proportions. Its origin dates back to the transmission to humans of retroviruses that infected populations of chimpanzees in central Africa approximately 100 years ago. From this location, its expansion to the whole world has been enormous, mainly in the last decades. Objectives: to carry out a literature review on the drug interaction between antiretrovirals and psychotropic drugs, identifying the factors that influence the consumption of psychotropic drugs in people with HIV. Method: Qualitative research, such as an integrative literature review, with data collected through articles available on online platforms. Results: The results obtained already published may be controversial, since some authors interpret certain adverse reactions as not resulting from drug interaction, but caused by the antidepressant, antipsychotic and antiretroviral drug itself, that is, the observation of effects side effects, which may be related both to the interaction of different classes of antiretrovirals and to that of antidepressants and antipsychotics with antiretrovirals, make it difficult to characterize the interaction and, therefore, this observation is often neglected. Conclusion: Despite the studies analyzed demonstrate effects between drug interactions (retrovirals and psychotropic drugs, research with a greater number of individuals should be developed. Introducción: El virus de la inmunodeficiencia humana tipo 1 (VIH-1) es el agente que produce el sida, enfermedad reconocida desde hace más de cuarenta años, que alcanzó proporciones pandémicas. Su origen se remonta a la transmisión a los humanos de retrovirus que infectan a las poblaciones de chimpancés en África central hace aproximadamente 100 años. Desde esta ubicación, su expansión a todo el mundo ha sido enorme, especialmente en las últimas décadas. Objetivos: Revisar la literatura sobre interacciones farmacológicas entre antirretrovirales y psicotrópicos, identificando los factores que influyen en el consumo de psicotrópicos en pacientes con VIH. Método: Investigación cualitativa, tipo revisión integradora de la literatura, con datos recolectados a través de artículos disponibles en plataformas online, google académico, Sciello (Scientific Electronic Library Online), Virtual Health Library (BVS); y LILACS (Literatura Latinoamericana en Ciencias de la Salud. Resultados: Los resultados obtenidos ya publicados pueden generar controversia, ya que algunos autores interpretan ciertas reacciones adversas como no debidas a interacción farmacológica, sino provocadas por el antidepresivo, antipsicótico y el propio fármaco. es decir, la observación de efectos secundarios, que pueden estar relacionados tanto con la interacción de diferentes clases de antirretrovirales como con la de antidepresivos y antipsicóticos con antirretrovirales, dificulta la caracterización de la interacción y, por lo tanto, esta observación a menudo se descuida. : Si bien los estudios analizados demuestran efectos entre interacciones medicamentosas (retrovirales y psicotrópicos), es necesario desarrollar investigaciones con un mayor número de individuos. Introdução: O vírus da imunodeficiência humana tipo 1 (HIV-1) é o agente que produz a AIDS, doença reconhecida há mais de quarenta anos, que atingiu proporções pandêmicas. Sua origem remonta à transmissão aos humanos de retrovírus que infectam populações de chimpanzés na África central há aproximadamente 100 anos. Deste local sua expansão para todo o mundo tem sido enorme, principalmente nas últimas décadas. Objetivos: Realizar revisão de literatura sobre a interação medicamentosa entre antirretrovirais e psicofármacos, identificando os fatores que influenciam o consumo de medicamentos psicotrópicos nos portadores de HIV. Metódo: Pesquisa qualitativa, do tipo revisão integrativa de literatura, com dados coletados através de artigos disponíveis nas plataformas online, google acadêmico, Sciello (Scientific Electronic Library Online) , Biblioteca Virtual em Saúde (BVS); e LILACS (Literatura Latino-Americana em Ciências da Saúde. Resultados: Os resultados obtidos já publicados podem gerar controvérsias, uma vez que alguns autores interpretam determinadas reações adversas como sendo não decorrentes de interação medicamentosa, e sim causadas pelo próprio fármaco antidepressivo, antipsicótico e antirretroviral isoladamente, ou seja, a observação de efeitos colaterais, que podem estar relacionados tanto com a interação de diferentes classes de antirretrovirais quanto com a de antidepressivos e antipsicóticos com antirretrovirais, dificulta a caracterização da interação e, por isso, essa observação é muitas vezes negligenciada. Conclusão: Apesar dos estudos analisados demostrarem efeitos entre a interação medicamentosa (retrovirais e psicofármacos), pesquisa com um maior número de indivíduos deve ser desenvolvidas.

Pharmaceutical analysis plays a very prominent role in quality assurance as well as quality control of bulk drugs and pharmaceutical formulations. Rapid increase in pharmaceutical industries and production of drug in various parts of the world has brought a rise in demand for new analytical techniques in the pharmaceutical industries. As a consequence, analytical method development has become the basic activity of analysis. From the times of yore, people were trying to find safe and sound ways to treat viral infections. In the current scenario, due to the emerging of new viruses, the development of drugs for their treatment is also gaining equal importance. Before launching to the market, these drugs should undergo a validation process. High-performance liquid chromatography (HPLC) coupled with ultraviolet (UV), Photodiode array detectors (PDA), Mass spectrophotometer (MS) detectors etc. is one of the fastest, safe and precise technologies used for determination and separation of pharmaceutical drugs, impurities and biological samples. HPLC is versatile and it takes less time for quantification of drugs as compared to old liquid chromatography techniques. Tenofovir disoproxil fumarate (TDF), Emtricitabine (FTC) and Efavirenz (EFV) is antiretroviral medicine used treat AIDS as well as chronic Hepatitis-B. It is used alone or with other HIV medications to help control HIV infection. The present review article assesses the published analytical methods and a variety of approach for investigation of TDF, FTC and EFV in bulk drug as well as pharmaceutical formulations including combinations. The present studies revealed that HPLC technique along with the spectroscopic have been most widely explored for the analysis. The investigatory review may provide the comprehensive details to the researchers who are working in the area of analytical research of TDF, FTC and EFV.

We report supramolecular repurposing of emtricitabine (FTC, trade name: Emtriva®), a blockbuster FDA-approved anti-HIV agent. FTC is revealed to act as a hydrogen-bonded cleft for bipyridine recognition. The supramolecular repurposing is realized by the generation of four cocrystals through liquid-assisted grinding. The clefts comprise discrete three-component assemblies sustained by a combination of hydrogen bonds and π⋯π interactions.

Viruses are the smallest infectious agents of animal and plant tissues. Viruses are totally dependent on living cells to survive as they utilize the host cell's own replication processes, in order to reproduce themselves. HIV is the causative agent of AIDS. HIV is an unusually difficult to treat because it incorporate its own genetic material into the genome of an infected host cell. It infects T cells that carry the CD4 antigen on their surface. Binding and fusion, reverse transcription, integration, transcription, assembly and budding are the major steps of the HIV life cycle. The HIV/AIDS disease is treated by interrupting the HIV life cycle with specially designed drugs. The discovery of effective drugs against HIV has focused on targeting various critical components of the replication cycle of HIV. Depending on the target within the HIV replicative cycle they interact with, anti-HIV compounds are categorized into six groups. These are: nucleoside (nucleotide) reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The development of effective anti-HIV drugs is difficult due to wide variations in nucleotide and amino acid sequences. The development of anti-HIV drug passes through several important steps. This includes development from α-APA to ITU, ITU to DATA, DAPY to etravirine. Fosdevirine, lersivirine and rilpivirine are among the drugs that were undergoing clinical development and finally only rilpivirine was approved by FDA. The synthesis of delavirdine employs the use of heterocyclic rings like substituted pyridine and indole.

At the health emergence, no such potent prophylactic therapy is available to control the deadly emerged Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, existing antiviral, anti-inflammatory, antimalarial drugs is the only option against SARS-CoV-2, but it may be harmful to patients without more clinical evidence. As an alternative solution, we proposed a newer hypothesis using the selective 10 potent anti-HIV drugs and flavonoid class of phytochemicals from previous reports to use in combination against SARS-CoV-2. Primarily, 10 anti-HIV protease inhibitor drugs and 10 phyto-flavonoids as ligands in molecular docking study against the putative target, the SARS-CoV-2-main protease (Mpro) ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, −10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, −10.90 kcal/mol and drug-likeness rating, 0.82) were selected for further analysis in combined effect. Perceptibly, the combined ‘anti-HIV drug and phyto-flavonoid’ docking complex has actively interacted with eight strong H-bonds with stability, briefly elucidated through RMRD-, RMSF- Rg-plots and MM/PBSA-binding energy calculation during 100 ns than the individual against SARS-CoV-2-Mpro. Thus, the ‘anti-HIV-drug-phyto-flavonoid’ combination therapy could be used against SARS-CoV-2 after some experimental validation. Communicated by Ramaswamy H. Sarma

Integrase strand transfer inhibitors (INSTIs) are currently recommended for the first line treatment of human immunodeficiency virus type one (HIV-1) infection. The first-generation INSTIs are effective but can select for resistant viruses. Recent advances have led to several potent second-generation INSTIs that are effective against both wild-type (WT) HIV-1 integrase and many of the first-generation INSTI-resistant mutants. The emergence of resistance to these new second-generation INSTIs has been minimal, which has resulted in alternative treatment strategies for HIV-1 patients. Moreover, because of their high antiviral potencies and, in some cases, their bioavailability profiles, INSTIs will probably have prominent roles in pre-exposure prophylaxis (PrEP). Herein, we review the current state of the clinically relevant INSTIs and discuss the future outlook for this class of antiretrovirals.

Introducción: El Rategravir pertenece a los inhibidores de integrasas, quedando demostrado y aprobado por diversos ensayos clínicos como un potente antirretroviral seguro y eficaz para el tratamiento de pacientes infectados con el virus de inmunodeficiencia humana (VIH), con buena tolerancia y baja toxicidad, incluyéndose en el esquema de tercera línea o rescate y se inicia cuando los esquemas de primera y segunda línea han fracasado. Objetivo: Evaluar la eficacia y seguridad en condiciones clínicas reales del uso de Raltegravir dentro de los esquemas de la Terapia Antiretroviral de Gran Actividad (TARGA) en pacientes con infección por VIH en un hospital de referencia del seguro social en Perú. Métodos: Se realizó un estudio observacional retrospectivo en pacientes con diagnóstico de infección por VIH que iniciaron tratamiento dentro del esquema TARGA basados en Raltegravir con seguimiento y control a los 6 meses. Se presentaron medidas de resumen de frecuencias y porcentajes para las variables cualitativas, así como medias y desviación estándar para las variables cuantitativas en base a los resultados de las pruebas de normalidad. Los datos fueron procesados y analizados en el software estadístico SPSS versión 22. Resultados: El género masculino fue el más afectado con un 76%(n=119) del total. El rango de edad más frecuente fue el comprendido entre los 45 a 55 años (25,4%; n=40). Las comorbilidades más frecuentes fueron Diabetes mellitus e Hipertensión arterial, con reducción exponencial de la carga viral y elevación de los niveles de linfocitos CD4. Conclusión: El Raltegravir es eficaz para el tratamiento de pacientes VIH. Introduction: Rategravir belongs to integrase inhibitors, being demonstrated and approved by several clinical trials as a powerful and safe antiretroviral drug for the treatment of patients infected with human immunodeficiency virus (HIV), with good tolerance and low toxicity, including in the third line or rescue scheme and it starts when the first and seconde line schemes have failed.Objective: To evaluate the efficacy and safety in real clinical conditions of the use of Raltegravir within the HAART schemes in patients with HIV infection in a reference hospital of social insurance in Peru.Methods: A retrospective observational study was performed in patients with a diagnosis of HIV infection who started treatment within the TARGA scheme based on Raltegravir with follow-up and control at 6 months. We presented summary measures of frequencies and percentages for the qualitative variables, as well as means and standard deviation for the quantitative variables based on the results of the normality tests. The data was processed and analyzed in the statistical software SPSS version 22.Results: The male gender was the most affected with 76% (n = 119) of the total. The most frequent age range was between 45 to 55 years (25.4%, n = 40). The most frequent comorbidities were Diabetes mellitus and arterial hypertension, with exponential reduction in viral load and elevation of CD4 lymphocyte levels.Conclusion: Raltegravir is effective for the treatment of HIV patients.

Background: Integrase (IN) is an essential protein for HIV replication that catalyzes insertion of the reverse-transcribed viral genome into the host chromosome during the early steps of viral infection. Highly active anti-retroviral therapy (HAART) is a HIV/AIDS treatment method that combines three or more antiviral drugs often formulated from compounds that inhibit the activities of viral reverse transcriptase and protease enzymes. Early IN inhibitors (INIs) mainly serve as integrase strand transfer inhibitors (INSTI) that disrupt strand transfer by binding the catalytic core domain (CCD) of IN. However, mutations of IN can confer resistance to INSTI. Therefore, non-catalytic integrase inhibitors (NCINI) have been developed as next-generation INIs. Methods: In this study, we evaluated and compared the activity of INSTI and NCINI according to the analysis method. Antiviral activity was compared using p24 ELISA with MT2 cell and TZM-bl luciferase system with TZM-bl cell. Each drug was serially diluted and treated to MT2 and TZM-b1 cells, infected with HIV-1 AD8 strain and incubated for 5 and 2 days, respectively. Additionally, to analyze properties of INSTI and NCINI, transfer inhibition assay and 3'-processing inhibition assay were performed. Results: During screening of INIs using the p24 ELISA and TZM-bl luciferase systems, we found an inconsistent result with INSTI and NCINI drugs. Following infection of MT2 and TZM-bl cells with T-tropic HIV-1 strain, both INSTI and NCINI treatments induced significant p24 reduction in MT2 cells. However, NCINI showed no antiviral activity in the TZM-bl luciferase system, indicating that this widely used and convenient antiretroviral assay is not suitable for screening of NCINI compounds that target the second round of HIV-1 replication. Conclusion: Accordingly, we recommend application of other assay procedures, such as p24 ELISA or reverse transcription activity, in lieu of the TZM-bl luciferase system for preliminary NCINI drug screening. Utilization of appropriate analytical methods based on underlying mechanisms is necessary for accurate assessment of drug efficacy.

SARS-related coronaviruses poses continual threat to humanity by rapidly mutating and emerging as severe pandemic outbreaks, including the current nCoV-19 pandemic. Hence a rapid drug repositioning and lead identification strategy are required to mitigate these outbreaks. We report a pharmacophore and molecular dynamics-based approach for drug repositioning and lead identification against dual targets (3CLp and PLp) of SARS-CoV-2. The pharmacophore model of 3CLp inhibitors was apolar with two aromatic and two H-bond acceptors, whereas that of PLp was relatively polar, bearing one aromatic and three H-bond acceptors. Pharmacophore-based virtual screening yielded six existing FDA-approved drugs and twelve natural products with both the pharmacophoric features. Among them are nelfinavir, tipranavir and licochalcone-D, which has shown better binding characteristics with both the proteases compared to lopinavir. The molecular dynamics revealed that the connecting loop (residues 176–199) of 3CLp is highly flexible, and hence, inhibitors should avoid high-affinity interactions with it. Lopinavir, due to its high affinity with the loop region, exhibited unstable binding. Further, the van der Waals size of the 3CLp inhibitors positively correlated with their binding affinity with 3CLp. However, the van der Waals size of a ligand should not cross a threshold of 572Å3, beyond which the ligands are likely to make high-affinity interaction with the loop and suffer unstable binding as observed in the case of lopinavir. Similarly, the total polar surface area of the ligands were found to be negatively correlated with their binding affinity with PLp., Graphical Abstract Communicated by Ramaswamy H. Sarma

The emergence of the pandemic coronavirus-2019 (COVID-19) disease by the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) or 2019-novel coronavirus-2019 (2019- nCoV-2019) has created a disease-ridden environment for the entire human community, globally. However, no potent prophylactic therapy is available to control the deadly emerged viral disease. Repurposing of existing antiviral, antiinflammatory, antimalarial drugs is the only option against SARS-CoV-2. But without any clinical evidence, the recommended dose and expected side effects are under debate. As an alternative solution, we proposed a newer hypothesis using the selective, potent anti-HIV drugs and flavonoid class of phytochemicals in combination to balance the potency and toxicity during combat against SARS-CoV-2. Primarily, ten anti-HIV protease inhibitor drugs with ten phyto-flavonoids are selected as ligands for docking study against the putative target, the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, -10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, -10.90 kcal/mol and drug-likeness rating, 0.82), were selected for further analysis in the mixture. Later, the interchanged mutual docking analysis suggested that ‘darunavir-quercetin-3- rhamnoside’ was the most potent and less toxic drug chemical-cocktail/ formulation against SARS-CoV-2-Mpro. Additionally, molecular dynamics simulation, predicted toxicity and pharmacokinetics profiles also support to the hypothesized formulation; mainly, eight strong H- bond interactions were found against SARS-CoV-2-Mpro. Thus, projected molecular docking- simulation based active and lesser toxic ‘anti-HIV-drug-phyto-flavonoid’ therapy could be promoted against SARS-CoV-2.

Hepatitis B virus (HBV), a small enveloped DNA virus, attacks the human liver causing both acute and chronic diseases. Current therapeutic drugs use the nucleos(t)ide analogues (NAs) as a competitive inhibitor against HBV reverse transcriptase (HBV-RT), an essential enzyme pivotally involved in viral replication. Unfortunately, this treatment still causes the development of resistant variants of HBV against NAs. As HBV-RT is homologous to the human immunodeficiency virus reverse transcriptase (HIV-RT), it is reasonable to treat HBV-RT with anti-HIV drugs. In the present study, we aimed to investigate the structural dynamics and susceptibility of the known anti-HIV drugs (stavudine [d4T], didanosine [DDI], and zidovudine [ZDV]) against HBV-RT enzyme in comparison to the anti-HBV drug lamivudine (3TC) and deoxythymidine triphosphate (dTTP) substrate using several computational approaches. The ΔGbindresidue calculations revealed that seven polar residues (K32, R41, D83, S85, D205, N236, and K239) and three hydrophobic residues (A86, A87, and F88) of HBV-RT as well as the adjacent DNA strands play an important role in the ligand binding. In addition, the H-bond pattern of d4T is similar to that of 3TC, especially at the residues A86 and A87. Such interactions promote the favorable conformation of ligand in the HBV-RT binding pocket, while the several different conformations of ligand are found in the unbound state. The predicted binding free energy results based on QM/MM-GBSA and MM/GB(PB)SA methods suggested that the susceptibility towards HBV-RT of d4T and ZDV is higher than that of 3TC and dTTP. Altogether, this work sheds light on the potentiality of d4T and ZDV as a promising drug for HBV-infected patients harboring 3TC resistance. Communicated by Ramaswamy H. Sarma

Bioisosteric replacement is a powerful tool for modulating the drug-like properties, toxicity, and chemical space of experimental therapeutics. In this review, we focus on selected cases where bioisosteric replacement and scaffold hopping have been used in the development of new anti-HIV-1 therapeutics. Moreover, we cover field-based, computational methodologies for bioisosteric replacement, using studies from our group as an example. It is our hope that this review will serve to highlight the utility and potential of bioisosteric replacement in the continuing search for new and improved anti-HIV drugs.

The synthetic peptide CIGB-210 is a promising anti-HIV drug candidate shown to inhibit HIV replication in MT4 cells at the nanomolar range by triggering the rearrangement of vimentin intermediate filaments. Sensitive and specific analytical methods are required for pharmacological studies of CIBG-210 in animals. In this study, we describe the development of a competitive ELISA for the quantitative determination of CIGB-210 using an anti-CIGB-210 hyperimmune serum. After optimization of all the steps, the assay exhibited a dynamic range from 11.87 to 0.0095 µg/mL. The intra-assay coefficient of variation (CV) was lower than or close to 5% for all the six concentrations of the calibrator, and the inter-assay CV was below 10% in five out of the six concentrations tested. No interference of either murine or human plasma was observed. The analyte was stable in plasma after five freeze-thaw cycles, while the hyperimmune serum maintained its binding capacity after 10 freeze-thaw cycles. Furthermore, the ELISA was able to detect the two main metabolites of CIGB-210, although with a tenfold decrease in sensitivity. Our results demonstrate the utility and feasibility of this analytical method for pharmacological experiments in animals as humans.

Molecular dynamics simulations for the structural complexes of potential HIV-1 inhibitors with the viral envelope gp120 protein were carried out. Free energies of the formation of these supramolecular structures and contributions of individual amino-acid residues of gp120 to the enthalpy binding were calculated. The residues of gp120 critical for interactions with the ligands were identified. Based on the data obtained, five compounds promising for synthesis and testing for antiviral activity were selected. It is suggested that these compounds may be successfully used in the design of novel, potent and broad anti-HIV drugs.

Nucleocapsid protein 7 (NCp7) represents a viable target not yet reached by the currently available antiretrovirals. It is a small and highly basic protein, which is essential for multiple stages of the viral replicative cycle, with its structure preserved in all viral strains, including clinical isolates. NCp7 can be inhibited covalently, noncovalently and by shielding the nucleic acid (NA) substrates of its chaperone activity. Although covalent NCp7 inhibitors have already been detailed in the first part of this review series, the focus here is based on noncovalent and NA-binder inhibitors and on the analysis of the NCp7 3D structure to deliver fruitful insights for future drug design strategies.

To deal with the rapid emergence of drug resistance challenges, together with the difficulty to eradicate the virus, off-target effects and significant cumulative drug toxicities, it is still imperative to develop next-generation anti-HIV agents with novel chemical classes or new mechanisms of action.We primarily focused on current strategies to discover novel anti-HIV agents. Moreover, examples of anti-HIV lead compounds were mainly selected from recently patented publications (reported between 2014 and 2017). In particular, 'privileged structure'-focused substituents decorating approach, scaffold hopping, natural-product diversification and prodrug are focused on. Furthermore, exploitation of new compounds with unexplored mechanisms of action and medicinal chemistry strategies to deplete the HIV reservoir were also described. Perspectives that could inspire future anti-HIV drug discovery are delineated.Even if a large number of patents have been disclosed recently, additional HIV inhibitors are still required, especially novel chemical skeletons displaying a unexploited mechanism of action. Current medicinal chemistry strategies are inadequate, and appropriate and new methodologies and technologies should be exploited to identify novel anti-HIV drug candidates in a time- and cost- effective manner.

HIV/AIDS continues to be one of the most challenging individual and public health concerns of our days [...]

Forming coordination complexes with nucleoside analogues may be helpful in studying anti-tumour activity of them. Therefore, to improve the clinical efficacy of nucleoside analogue and design new ones, a new fluorescent platinum (Pt) complex with anti-human immunodeficiency virus drug didanosine (ddI); K[PtCl(OCH3)2(ddI)]; was synthesized and characterized. The ultraviolet–visible (UV-vis) spectroscopy, infrared, thermogravimetric analysis, mass assignments and elemental analysis confirmed the preparation of the complex. The molecular ion peaks seen at the positive mass spectrum of Pt complex confirm coordination of the drug to metal centre. The interaction of this complex with calf thymus DNA (ct-DNA) was studied using several spectroscopic techniques such as UV absorption, fluorescence spectroscopy and dynamic viscosity measurements. Hyperchromism of the band in the UV-vis spectra and the intrinsic binding constant (0.56 ± 0.25) × 104 M−1, decreasing in Hoechst-DNA fluorescence by adding Pt complex concentration and also relatively small changes in DNA viscosity indicated that this complex could interact as a groove-binder. According to the UV spectra and the fluorescence quenching of the complex in our case seems to be primarily caused by complex formation between the Pt complex and DNA. The thermodynamic parameters showed that hydrogen bond and van der Waals interactions play main roles in the binding of Pt complex to ct-DNA. The free energy values are negative, showing the spontaneity of the Pt complex–DNA binding. The docking simulation was performed and the results confirm a preference of groove site of synthesized complex on DNA helix. The knowledge gained from this study will be helpful to further understand the DNA binding mechanism and can also provide much fruitful information for designing a new type of anti-cancer drugs. Communicated by Ramaswamy H. Sarma

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina Apesar de todos os avanços realizados na últimas décadas, a infeção pelo Vírus da Imunodeficiência Humana (VIH) em idade pediátrica continua a ser uma realidade em todo o mundo, sendo que, atualmente, a vasta maioria dos casos é devida a transmissão mãe-filho. As estratégias preventivas, com destaque para profilaxia pós-exposição neonatal com antirretrovíricos, assumem um papel fulcral na diminuição de novas infeções, possibilitando uma oportunidade única para a eliminação desta doença em gerações futuras. O objetivo deste trabalho foi analisar as últimas publicações e recomendações internacionais, no que diz respeito às diferentes estratégias profiláticas de prevenção da transmissão do VIH mãe-filho. Foram incluídos artigos em língua inglesa publicados desde o ano de 1994, tendo sido dado maior importância àqueles publicados desde o ano de 2010. Recomendações portuguesas e internacionais foram consultadas e incluídas na análise. Em 1994 comprovou-se, pela primeira vez, que a zidovudina era eficaz na diminuição da transmissão do VIH, com redução de 70%, em comparação com o grupo sem intervenção terapêutica. Desde então, outras estratégias a vários níveis têm vindo a ser continuamente desenvolvidas, com o intuito de minimizar ainda mais este risco. Atualmente, se todas estas forem cumpridas, as taxas de transmissão são inferiores a 1%. Contudo, existem ainda obstáculos que devem ser ultrapassados a nível mundial, no caminho para a eliminação desta doença, tal como a heterogeneidade a nível dos diversos países, no que diz respeito a algumas intervenções específicas. Na sequência desta análise, de forma a sistematizar a informação, foi elaborada uma proposta de revisão do protocolo de profilaxia e seguimento de recém-nascidos expostos ao VIH materno. Despite all the the advances in the last decade, particularly in developed countries, pediatric Human Imunodeficiency Virus (HIV) infection is still a reality all across the world and the large majority of cases is due to mother-to-child transmission. Preventive strategies, namely neonatal post-exposure prophylaxis with anti-HIV drugs, have a crucial role in the reduction of new infections, allowing an unique opportunity to eliminate this disease in future generations. The aim of this review is to analyze the latest findings and international recommendations regarding the different strategies for preventing mother-to-child transmission of HIV. We performed a literature search on the online libraries and articles in English since the year 1994 were included and we gave a higher degree of importance to the ones published since the year 2010. Portuguese and international guidelines were searched and included in the analysis.In 1994, for the first time, it was proven that zidovudine was effective in reducing mother-to-child transmission of HIV, in a rate of 70%, compared to a group without therapeutic intervention. Since then, multiple other strategies on various levels have been continuously developed with the aim of further reducing this risk. Nowadays, if these are correctly put to practice, rates of vertical transmission can be lower than 1%. However, there are still many obstacles that must be overcome globaly, in order to eliminate this disease. Heterogeneity between countries in regards to specific interventions also exists. We also propose a review of the protocol for prophylaxis and management to be used in neonates exposed to maternal HIV infection.