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Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.

The molecularly imprinted polymeric microspheres (MIPMs, 3∼5 μm), used as high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) packing materials for anti-AIDS drug emtricitabine (FTC), were synthesized by precipitation polymerization. The effects of ratio of chloroform to acetonitrile on the morphology and diameter of MIPMs were investigated. The prepared MIPMs were characterized by HPLC. The imprinting factor (2.26) suggests that the resultant MIPMs exhibit good recognition and affinity to FTC. In addition, the MIPMs were used in SPE as packing material for separation and enrichment of FTC. The recovery of FTC on MIPMs cartridge was 97.6 % in standard solution. Finally, the MIPMs cartridge was applied to extract the FTC in human serum samples. Impurities in sample have been mostly removed, and the average recovery of 92.5 % was obtained with a detection limit of 0.005 μg/mL and a linear range of 0.02∼4.0 μg/mL. The method established can be used to monitor the FTC in human serum sample with good accuracy and selectivity.

An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is integration of the double-stranded retroviral DNA into the genome of the host cell. HIV-1 integrase, the enzyme that inserts the vital DNA into the host chromosome, is an attractive and rational target for anti-AIDS drug design because it is essential for HIV replication and there are no known counterparts in the host cell. Inhibitors of this enzyme have the great potential to complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. Natural products have provided a source of new drug candidates for anti-AIDS therapy. Baicalein and baicalin, identified components of a Chinese herbal medicine Scutellaria baicalensis Georgi, have been shown to inhibit infectivity and replication of HIV. They are therefore promising lead compounds for developing new anti-AIDS drugs. To understand how the inhibitors work and therefore design more potent and specific inhibitors, we have used molecular modeling techniques to investigate the binding modes of these inhibitors. The three-dimensional structures of these inhibitors were first built. Then, computational binding studies of these inhibitors, based on the crystal structure of the HIV-1 integrase catalytic domain, were performed to study the complex structure. The preliminary results of our computational modeling study demonstrated that Baicalein binds to the active site region of the HIV-1 integrase. Our study will be of help to identify the pharmacophores of inhibitors binding to HIV-1 integrase and design new pharmaceuticals for the treatment of AIDS.

Accelerating education sector responses to HIV in Sub-Saharan Africa. This report examines the education sector's role in preventing HIV/AIDS and supporting affected communities. It's for educators, policymakers, and development professionals seeking effective strategies. Discover five years of experience in Sub-Saharan Africa, revealing successful approaches to HIV/AIDS prevention in schools. Learn how to implement policies, train teachers, and engage communities. Understand how coordinated efforts and resource allocation can create sustainable education programs, offering hope and empowerment to future generations. This is a crucial resource for building a stronger, healthier future.

Evidence is presented that a major class of drugs, the dideoxynucleosides (ddNs) and nucleoside/nucleotide analogues, may inhibit the symptoms of acquired immunodeficiency syndrome (AIDS) by initiation of inactivation at the ribonucleotide reductase (RNR) enzyme stage and/or inactivation of reverse transcriptase enzyme or at a stage more initial than that of the currently accepted DNA chain termination hypothesis. For example, it has been previously shown that ribonucleotide diphosphate reductase (RDPR) and ribonucleotide triphosphate reductase (RTPR) are inactivated with 2′-chloro-2 ‘-deoxyuridine 5′-diphosphate-([3′- 3 H]ClUDP) and triphosphate ([3′- 3 H]ClUTP) by reaction with an intermediate furanone, Scheme 2. RDPR has also been inactivated by 2 ‘ -azido-2 ‘ -deoxyuridine 5 ‘ -diphosphate (N3UDP). Furthermore, addition of hydroxyurea to RNR can inhibit DNA synthesis which results in a rapid depletion of limiting deoxynucleotide triphosphate (dNTP) pools. There are similar perturbations of dNTP pools upon interaction of human RNR with 3 ‘ -azido-2 ‘ ,3 ‘ -dideoxythymidine (AZT), in human cell studies involving AZT/HIV and in adenosine/coformycin experiments in relation to inherited immunodeficiency, Table 1. Also, the herein proposed reduction mechanisms of nucleotides by RNR ( e.g., a single electron transfer from the nucleotide base to the phenol moiety of the tyrosyl radical of RNR via a pathway involving the thiyl radical of a cysteine residue) can also account for the chemistry of some antiretroviral drugs, the ddNs. Analyses are presented that the RNR reductions of regular unsubstituted nucleotides may occur predominantly via initial 2’ C-H abstraction instead of the originally proposed 3’ C-H abstraction mechanism. Also, it is noted that the fate of the phenol moiety of the tyrosyl unit in some RNR reactions with 2 ‘ -halo-2 ‘ -deoxynucleotides is not clear. The proposed reaction mechanisms may provide guidance for the development of potentially effective anti-AIDS drugs.

'The Africa Multi-Country AIDS Program 2000-2006' shows that the funding made available through the World Bank's Multi-Country AIDS Program (MAP) has dramatically increased access to HIV prevention, care, and treatment across Africa.

The crystal and molecular structures of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine have been determined by x-ray diffraction and stereochemical comparisons with thymidine have been made. Atomic charge distributions have been calculated by the complete neglect of differential overlap method for thymidine and antiretrovirally active and inactive C3'-substituted analogues. The structural and electronic results suggest that antiviral activity in these analogues may be correlated with the presence of an electronegative atom attached to C3'.

Although HIV prevalence in South Asia is relatively low, the epidemic is growing among marginalized groups, including sex workers, injection drug users, men who have sex with men, and transgender communities. Despite prevention and other efforts to reduce high-risk behaviors such as unprotected sex, buying and selling of sex, and injecting drug use, HIV vulnerability and risk remain high. This problem is partly due to a widespread failure to respond adequately to key social drivers of HIV: stigma and discrimination. Stigmatizing attitudes in the general population and discriminatory treatment by actors ranging from health providers to local policy makers intensify the marginalization of vulnerable groups at highest risk, driving them further from the reach of health services and much-needed prevention, treatment, care, and support. Daily harassment and abuse also cause health problems and adversely affect mental health, thereby leading to depression, social isolation, and an array of adverse socioeconomic outcomes related to HIV and AIDS. The South Asia Region Development Marketplace1 (SARDM) took an innovative and unique approach to addressing these gaps and needs through its 2008 development marketplace, \"tackling HIV and AIDS stigma and discrimination.\" Part one of this reports describes key findings and lessons learned that emerged across the 26 implementers. Part two contains case studies for six of the implementers, offering a more in-depth look at the lessons and challenges of intervening against stigma and discrimination. Part three provides summaries of all 26 projects.

Anarchists have been central in helping communities ravaged by disasters, stepping in when governments wash their hands of the victims. Looking at Hurricane Sandy, Covid-19, and the social movements that mobilised relief in their wake, Disaster Anarchy is an inspiring and alarming book about collective solidarity in an increasingly dangerous world. As climate change and neoliberalism converge, mutual aid networks, grassroots direct action, occupations and brigades have sprung up in response to this crisis with considerable success. Occupy Sandy was widely acknowledged to have organised relief more effectively than federal agencies or NGOs, and following Covid-19 the term 'mutual aid' entered common parlance. However, anarchist-inspired relief has not gone unnoticed by government agencies. Their responses include surveillance, co-option, extending at times to violent repression involving police brutality. Arguing that disaster anarchy is one of the most important political phenomena to emerge in the twenty-first century, Rhiannon Firth shows through her research on and within these movements that anarchist theory and practice is needed to protect ourselves from the disasters of our unequal and destructive economic system.

Peter Piot, founding executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), recounts his experience as a clinician, scientist, and activist fighting the disease from its earliest manifestation to today. The AIDS pandemic was not only catastrophic to the health of millions worldwide but also fractured international relations, global access to new technologies, and public health policies in nations across the globe. As he struggled to get ahead of the disease, Piot found science does little good when it operates independently of politics and economics, and politics is worthless if it rejects scientific evidence and respect for human rights. Piot describes how the epidemic altered global attitudes toward sexuality, the character of the doctor-patient relationship, the influence of civil society in international relations, and traditional partisan divides. AIDS thrust health into national and international politics where, he argues, it rightly belongs. The global reaction to AIDS over the past decade is the positive result of this partnership, showing what can be achieved when science, politics, and policy converge on the ground. Yet it remains a fragile achievement, and Piot warns against complacency and the consequences of reduced investments. He refuses to accept a world in which high levels of HIV infection are the norm. Instead, he explains how to continue to reduce the incidence of the disease to minute levels through both prevention and treatment, until a vaccine is discovered.