The HIV-1 capsid protein plays a crucial role in viral infectivity, assembling into a fullerene cone that encloses the viral RNA and it has gained attention as a promising therapeutic target. Research has been focused on the spatial structures of capsid proteins in recent years, and peptides and small molecules targeting capsid have been discovered. In this article, it summarizes the structure information of capsid protein, analyzes and compares the binding information of different peptides and small molecules targeting capsid. At the same time we give the perspective to the future drug discovery based on the protein-protein interaction during the maturation process.
Capsid ; chemistry ; Drug Discovery ; HIV Infections ; drug therapy ; HIV-1 ; chemistry

Racemic (±)-F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide A), an analog of nature product (+)-calanolide A, is a new anti-HIV-1 nonnucleoside reverse transcript inhibitor (NNRTI). A successful enantioseparation of (±)-F18 offering (R)-F18 and (S)-F18 was achieved by a chiral stationary phase prepared HPLC. Their absolute configurations were determined by measurement of their electronic circular dichroisms combined with modem quantum-chemical calculations. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses.
Anti-HIV Agents ; chemistry ; Chromatography, High Pressure Liquid ; HIV-1 ; drug effects ; Pyranocoumarins ; chemistry

A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
AIDS Vaccines ; chemistry ; immunology ; Antibodies, Neutralizing ; immunology ; HIV Antibodies ; immunology ; HIV Envelope Protein gp41 ; immunology ; HIV-1 ; chemistry ; immunology ; Humans

Alleles ; Crystallography, X-Ray ; HIV Infections ; HIV-1 ; HLA-B Antigens ; chemistry ; immunology ; Humans

LEDGF/p75 is a newly found cell cofactor, which plays an essential role in the integration of HIV-1 cDNA into host chromosomes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells or over-expressing the integrase-binding domain of LEDGF/p75 blocks viral replication. The essential role of LEDGF/p75 in HIV-1 replication makes it a new target for anti-HIV-1 drug development. This article reviews the function of LEDGF/p75, LEDGF/p75-integrase interaction and LEDGF/p75 inhibitors.
Anti-HIV Agents ; chemistry ; pharmacology ; HIV Integrase ; metabolism ; HIV-1 ; drug effects ; physiology ; Intercellular Signaling Peptides and Proteins ; metabolism ; Protein Binding

Animals ; Anti-HIV Agents ; chemistry ; pharmacology ; Furans ; pharmacology ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Keto Acids ; chemistry ; pharmacology ; Molecular Structure ; Naphthyridines ; pharmacology ; Triazoles ; pharmacology

Both reverse transcriptase (RT) and integrase (IN) play crucial roles in the life cycle of HIV-1, which are also key targets in the area of anti-HIV drug research. Reverse transcriptase inhibitors are involved in the most employed drugs used to treat AIDS patients and HIV-infected people, while one of the integrase inhibitors has already been approved by US FDA to appear on the market. Great achievement has been made in the research on both, separately. Recently, much more attention of medicinal chemistry researchers has been attracted to the strategies of multi-target drugs. Compounds with excellent potency against both HIV RT and IN, evidently defined as dual inhibitors targeting both enzymes, have been obtained through considerable significant exploration, which can be classified into two categories according to different strategies. Combinatorial chemistry approach together with high throughput screening methods and multi-target-based virtual screening strategy have been useful tools for identifying selective anti-HIV compounds for long times; Rational drug design based on pharmacophore combination has also led to remarkable results. In this paper, latest progress of both categories in the discovery and structural modification will be covered, with a view to contribute to the career of anti-HIV research.
Drug Design ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; HIV Reverse Transcriptase ; antagonists & inhibitors ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Reverse Transcriptase Inhibitors ; chemistry ; pharmacology ; Structure-Activity Relationship

HIV-1 integrase (IN) is an essential enzyme for retroviral replication. There is no analogue for this enzyme in human cells so that inhibition of IN will not bring strong effect on human body. Thus, HIV-1 IN has become a rational target for therapy of AIDS. This review provides a comprehensive report of alpha, gamma-diketo IN inhibitors discovered in recent years. Compilation of such data will prove to be beneficial in developing QSAR, pharmacophore hypothesis generation and validation, virtual screening and synthesis of compounds with higher activity.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; HIV Integrase ; chemistry ; physiology ; HIV Integrase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Keto Acids ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Quantitative Structure-Activity Relationship

OBJECTIVETo develop a rapid test kit for antibody to HIV by nano immunomagnetic lateral flow method.

METHODSA rapid test kit was developed by conjugation of the HIV antigen gp41 and gp36 to 200nm super paramagnetic particles by carbodiimide (EDC) and coating of the HIV antigen gp41 and gp36 to nitrocellulose membrane. Then the kit was evaluated with serials of experiments.

RESULTSThe kit was qualified with examination of national reference panel of anti-HIV antibody for colloidal gold diagnostic kit. The sensitivity was 100% by tested with 20 HIV antibody positive sera, the specificity was 98.5% by tested with 600 HIV antibody negative sera, respectively. The stability of the kit was over 12 month by storage at room temperature.

CONCLUSIONA diagnostic kit for antibody to HIV was developed with the advantages of convenience, rapid test, good stability and point of care.

Antibodies, Anti-Idiotypic ; immunology ; Gold Colloid ; chemistry ; HIV ; immunology ; isolation & purification ; HIV Antibodies ; HIV Envelope Protein gp41 ; HIV Infections ; diagnosis ; HIV Seropositivity ; blood ; HIV-1 ; immunology ; isolation & purification ; Immunomagnetic Separation ; methods ; Molecular Biology ; methods ; Nanotechnology ; Reagent Kits, Diagnostic

HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Resistance, Multiple ; HIV Envelope Protein gp41 ; chemical synthesis ; chemistry ; pharmacology ; HIV Fusion Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; physiology ; Humans ; Peptide Fragments ; chemical synthesis ; chemistry ; pharmacology ; Peptides ; chemical synthesis ; chemistry ; pharmacology ; Recombinant Fusion Proteins ; chemical synthesis ; chemistry ; pharmacology ; Virus Replication ; drug effects ; alpha 1-Antitrypsin ; chemical synthesis ; chemistry ; pharmacology