Inhibition Of Human Immunodeficiency Virus Research Articles

Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity.

Recent advances in the development of antiretrovirals have significantly extended life-spans and positively impacted morbidity of HIV-seropositive patients. While effective, antiretrovirals are associated with complex medication regimens, large pill burdens, and significant side effects which may impact quality of life. Researchers continue to examine various chemical entities in their search for agents with anti-HIV activity. Ideal agents would be efficacious, easily dosed and administered, inexpensive, and with few adverse effects. Chloroquine and its analog hydroxychloroquine are two inexpensive agents that are widely used for the treatment of malaria and have been shown to achieve some level of anti-HIV activity. The exact mechanism of chloroquine and hydroxychloroquine's anti-HIV activity has not yet been discerned but may be related to effects on HIV's surface envelope glycoprotein 120. If found efficacious, both drugs would offer significant advantages to current therapy including a unique mechanism of action, lack of cross-resistance with other antiretrovirals, and low cost. Early and limited in vitro and in vivo data have demonstrated modest anti-HIV efficacy as indicated by measures of viral burden. Effects on CD4+ cell counts have not been as pronounced. It is premature to advocate the use of either of these agents in the management of routine HIV disease; however; the drugs should be further studied to determine their benefit in the treatment of patients who have exhausted all standard treatments. Larger, well-controlled trials are needed to discern the potential role of chloroquine and hydroxychloroquine in the management of HIV.

Antisense-mediated inhibition of human immunodeficiency virus (HIV) replication by use of an HIV type 1-based vector results in severely attenuated mutants incapable of developing resistance.

We have constructed a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector expressing a 937-base antisense sequence against the HIV-1 envelope gene. Transduction of CD4(+) T lymphocytes with this vector results in expression of the therapeutic antisense sequence and subsequent inhibition of productive HIV-1 replication. In this report, we examined the effect of antisense-mediated suppression on the potential development of virus escape mutants using a permissive T-cell line cultured under conditions that over serial passages specifically allowed for generation and amplification of mutants selected for by antisense pressure. In the resulting virus clones, we found a significant increase in the number of deletions at the envelope target region (91% compared to 27.5% in wild-type HIV). Deletions were most often greater than 1 kb in length. These data demonstrate for the first time that during antisense-mediated suppression of HIV, mutants develop as a direct result of selective pressure on the HIV genomic RNA. Interestingly, in clones where deletions were not observed, there was a high rate of A-G transitions in mutants at the antisense target region but not outside this region, which is consistent with those mutations that are predicted as a result of antisense-mediated modification of double-stranded RNA by the enzyme double-stranded RNA-specific adenosine deaminase. These clones were not found to be escape mutants, as their replicative ability was severely attenuated, and they did not replicate in the presence of vector.

Mini ReviewThe Effect of Interleukin-16 and its Precursor on T Lymphocyte Activation and Growth

Interleukin-16 (IL-16) was the first described T lymphocyte chemoattractant. It has since been shown that IL-16 also functions as a primer of T cell proliferation, a modulator of inflammatory and immune responses, a stimulus of B cell differentiation and an inhibitor of Human immunodeficiency virus (HIV) replication. Its precursor, Prointerleukin-16 (pro-IL-16), is expressed in both the nucleus and cytoplasm of T cells. Cytoplasmic pro-IL-16 serves as the precursor for mature IL-16 while nuclear pro-IL-16 is associated with G0/G1 cell cycle arrest. Herein, we review the ability of IL-16 to act as both primer and modulator of T lymphocyte growth. The impact of IL-16 on T cell apoptosis is also discussed. Finally, we describe the role of pro-IL-16 as a T lymphocyte cell cycle growth suppressor.

Human immunodeficiency virus type 1 (HIV-1) integrase: resistance to diketo acid integrase inhibitors impairs HIV-1 replication and integration and confers cross-resistance to L-chicoric acid.

The diketo acids are potent inhibitors of human immunodeficiency virus (HIV) integrase (IN). Mutations in IN, T66I, S153Y, and M154I, as well as T66I-S153Y and T66I-M154I double mutations, confer resistance to diketo acids (D. J. Hazuda et al., Science 287:646-650, 2000). The effects of these IN mutations on viral replication, enzymatic activity, and susceptibility to other HIV inhibitors are reported herein. By immunofluorescence assay and real-time PCR, all mutant viruses demonstrated a modest delay in viral spread compared to that of reference HIV. These viruses also showed a statistically significant defect in integration without defects in reverse transcription. Recombinant IN containing S153Y, T66I, and M154I-T66I mutations had an approximately twofold decrease in both disintegration and 3'-end-processing-strand transfer activities in vitro. In contrast, IN containing M154I demonstrated a greater than twofold increase in specific activity in both reactions. All mutant HIVs were resistant to l-chicoric acid, a dicaffeoyltartaric acid IN inhibitor, both in tissue culture and in biochemical assays, yet remained susceptible to the reverse transcriptase inhibitors zidovudine and nevirapine. Thus, IN mutations conferring resistance to the diketo acids can yield integration defects, attenuated catalysis in vitro, and cross-resistance to l-chicoric acid.

Attenuation of HIV-1 Replication in Primary Human Cells with a Designed Zinc Finger Transcription Factor

Small molecule inhibitors of human immunodeficiency virus, type 1 (HIV-1) have been extremely successful but are associated with a myriad of undesirable effects and require lifelong daily dosing. In this study we explore an alternative approach, that of inducing intracellular immunity using designed, zinc finger-based transcription factors. Three transcriptional repression proteins were engineered to bind sites in the HIV-1 promoter that were expected to be both accessible in chromatin structure and highly conserved in sequence structure among the various HIV-1 subgroups. Transient transfection assays identified one factor, KRAB-HLTR3, as being able to achieve 100-fold repression of an HIV-1 promoter. Specificity of repression was demonstrated by the lack of repression of other promoters. This factor was further shown to repress the replication of several HIV-1 viral strains 10- to 100-fold in T-cell lines and primary human peripheral blood mononuclear cells. Repression was observed for at least 18 days with no significant cytotoxicity. Stable T-cell lines expressing the factor also do not show obvious signs of cytotoxicity. These characteristics present KRAB-HLTR3 as an attractive candidate for development in an intracellular immunization strategy for anti-HIV-1 therapy.

HIV entry and fusion inhibitors.

Human immunodeficiency virus (HIV) is a retrovirus that is the causative agent of acquired immunodeficiency syndrome (AIDS). Current HIV therapy is based on targeting two critical enzymes in the viral replication machinery: reverse transcriptase and a virally encoded protease. Although mortality rates due to HIV infection have been dramatically reduced, AIDS remains a major health problem throughout the world. The emergence of HIV variants that are resistant to current therapies and potential toxicity associated with their chronic use has highlighted the need for new approaches to HIV inhibition. Identification of the mechanisms underlying viral entry into the host cell has provided a number of novel therapeutic targets and the first of these HIV fusion inhibitors (enfuvirtide [pentafuside, T-20, Fuzeon; Roche Laboratories and Trimeris]) has recently been approved in the US and Europe. This review will focus on recent progress in the development of therapeutics that target the HIV entry process.

Shikonin, a component of chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1.

Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities, including inhibition of human immunodeficiency virus (HIV) type 1 (HIV-1). G protein-coupled chemokine receptors are used by HIV-1 as coreceptors to enter the host cells. In this study, we assessed the effects of shikonin on chemokine receptor function and HIV-1 replication. The results showed that, at nanomolar concentrations, shikonin inhibited monocyte chemotaxis and calcium flux in response to a variety of CC chemokines (CCL2 [monocyte chemoattractant protein 1], CCL3 [macrophage inflammatory protein 1alpha], and CCL5 [regulated upon activation, normal T-cell expressed and secreted protein]), the CXC chemokine (CXCL12 [stromal cell-derived factor 1alpha]), and classic chemoattractants (formylmethionyl-leucine-phenylalanine and complement fraction C5a). Shikonin down-regulated surface expression of CCR5, a primary HIV-1 coreceptor, on macrophages to a greater degree than the other receptors (CCR1, CCR2, CXCR4, and the formyl peptide receptor) did. CCR5 mRNA expression was also down-regulated by the compound. Additionally, shikonin inhibited the replication of a multidrug-resistant strain and pediatric clinical isolates of HIV in human peripheral blood mononuclear cells, with 50% inhibitory concentrations (IC(50)s) ranging from 96 to 366 nM. Shikonin also effectively inhibited the replication of the HIV Ba-L isolate in monocytes/macrophages, with an IC(50) of 470 nM. Our results suggest that the anti-HIV and anti-inflammatory activities of shikonin may be related to its interference with chemokine receptor expression and function. Therefore, shikonin, as a naturally occurring, low-molecular-weight pan-chemokine receptor inhibitor, constitutes a basis for the development of novel anti-HIV therapeutic agents.

Inhibition of human immunodeficiency virus by a new class of pyridine oxide derivatives.

A new class of pyridine oxide derivatives as inhibitors of human immunodeficiency virus type 1 (HIV-1) and/or HIV-2 replication in cell culture has been identified. The compounds, which specifically inhibit HIV-1, behave as typical nonnucleoside reverse transcriptase inhibitors (NNRTIs). The most active congener of this group, JPL-133 (UC-B3096), has a 50% effective concentration of 0.05 microg/ml for HIV-1(III(B)) with a selectivity index of approximately 760 in CEM cell cultures. However, the cytostatic activity of most pyridine oxide derivatives highly depended on the nature of the cell line. All compounds, including those pyridine oxide derivatives that inhibit both HIV-1 and HIV-2 replication, select for NNRTI-characteristic mutations in the HIV-1 reverse transcriptase of HIV-infected cell cultures (i.e., Lys103Asn, Val108Ile, Glu138Lys, Tyr181Cys and Tyr188His). These amino acid mutations emerged mostly through transition of guanine to adenine or adenine to guanine in the corresponding codons of the reverse transcriptase (RT) gene. The HIV-1-specific pyridine oxide derivatives lost their antiviral activity against HIV-1 strains containing these mutations in the RT. However, most compounds retained pronounced antiviral potency against virus strains that contained other NNRTI-characteristic RT mutations, such as Leu100Ile and Val179Asp. Furthermore, the complete lack of inhibitory activity of the pyridine oxide derivatives against recombinant HIV-2 RT and partial retention of anti-HIV-1 activity against HIV-1 strains that contain a variety of HIV-1-characteristic mutations suggest that the pyridine oxide derivatives must have a second target of antiviral action independent from HIV-1 RT.

Comparative QSAR Based on Neural Networks for the Anti-HIV Activity of HEPT Derivatives

Among the non-nucleoside reverse transcriptase inhibitors, 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine (HEPT) derivatives have proved to be potent and selective inhibitors of human immunodeficiency virus (HIV-1). They are able to completely suppress virus replication in cell cultures. The quantitative structure-activity relationships (QSAR) try to describe the association between biological activities of a group of congeners and their molecular descriptors. In this paper, recent works on the application of neural networks (NN) and multiple regression analyses to quantitative structure-anti-HIV activity of HEPT derivatives are reviewed. NN have their origins in efforts to reproduce computer models of the information processing that takes place in the brain. They have found application in a wide variety of fields, such as image analysis of facial features, stock market predictions, etc. Application of the NN methods to problems in chemistry and biochemistry has rapidly gained popularity in recent years. We briefly describe a methodology for designing NN for QSAR and estimating their performances, and apply this approach to the prediction of anti-HIV activity of HEPT. The predictive power of the NN used is compared with that of other statistical methods.

Structural Analysis of the Epitope of the Anti-HIV Antibody 2F5 Sheds Light into Its Mechanism of Neutralization and HIV Fusion

Inhibition of human immunodeficiency virus (HIV) fusion with the host cell has emerged as a viable therapeutic strategy, and rational design of inhibitors and vaccines, interfering with this process, is a prime target for antiviral research. To advance our knowledge of the structural biology of HIV fusion, we have studied the membrane-proximal region of the fusogenic envelope subunit gp41, which includes the epitope ELDKWA of the broadly neutralizing human antibody 2F5. The structural evidence available for this region is contradictory, with some studies suggesting an overall helical conformation, while the X-ray structure of the ELDKWAS peptide bound to the antibody shows it folded in a type I β turn. We used a two-step strategy: Firstly, by a competition binding assay, we identified the proper boundaries of the domain recognized by 2F5, which we found considerably larger than the ELDKWAS hexapeptide. Secondly, we studied the structure of the resulting 13 amino acid residue peptide by collecting NMR data and analyzing them by our previously developed statistical method (NAMFIS). Our study revealed that the increase in binding affinity goes in parallel with stabilization of specific local and global conformational propensities, absent from the shorter epitope. When compounded with the available biological evidence, our structural analysis allows us to propose a specific role for the membrane-proximal region during HIV fusion, in terms of a conformational transition between the turn and the helical structure. At the same time, our hypothesis offers a structural explanation for the mechanism of neutralization of mAb 2F5.

CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from α-Defensin-1 HIV Inhibition

CD8(+) T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that alpha-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether alpha-defensins, particularly alpha-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant alpha-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8(+) cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with alpha-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, alpha-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, alpha-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8(+) cells with potent HIV-1 inhibitory activity and a neutralizing antibody against alpha-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that alpha-defensin-1 inhibits HIV-1 infection following viral entry but that alpha-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.

Human immunodeficiency virus type 1 entry inhibitors selected on living cells from a library of phage chemokines.

The chemokine receptors CCR5 and CXCR4 are promising non-virus-encoded targets for human immunodeficiency virus (HIV) therapy. We describe a selection procedure to isolate mutant forms of RANTES (CCL5) with antiviral activity considerably in excess of that of the native chemokine. The phage-displayed library of randomly mutated and N-terminally extended variants was screened by using live CCR5-expressing cells, and two of the selected mutants, P1 and P2, were further characterized. Both were significantly more potent HIV inhibitors than RANTES, with P2 being the most active (50% inhibitory concentration of 600 pM in a viral coat-mediated cell fusion assay, complete protection of target cells against primary HIV type 1 strains at a concentration of 10 nM). P2 resembles AOP-RANTES in that it is a superagonist of CCR5 and potently induces receptor sequestration. P1, while less potent than P2, has the advantage of significantly reduced signaling activity via CCR5 (30% of that of RANTES). Additionally, both P1 and P2 exhibit not only significantly increased affinity for CCR5 but also enhanced receptor selectivity, retaining only trace levels of signaling activity via CCR1 and CCR3. The phage chemokine approach that was successfully applied here could be adapted to other chemokine-chemokine receptor systems and used to further improve the first-generation mutants reported in this paper.

Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.

Beneficial effects of l-carnitine in myoblastic C2C12 cells : Interaction with zidovudine

l-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable l-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing l-carnitine. After intestinal absorption or hepatic biosynthesis, l-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side effects, including induction of myopathy characterized by a metabolic mitochondria dysfunction and a diminution of the muscle l-carnitine content. In this study, we described the characteristics of l-carnitine transport in C2C12 cells. We also demonstrated that zidovudine inhibited the l-carnitine transporter. This inhibition led to a significant reduction of the muscle cell growth. In C2C12 cells, the supplementation of l-carnitine prevented the effects of zidovudine and restored the normal cell growth.

Inhibition of human immunodeficiency virus 1 replication in vitro by a self-stabilized oligonucleotide with 2'-O-methyl-guanosine-uridine quadruplex motifs.

Given that the guanosine-quadruplex may have a role in blocking the interaction between gp120 and CD4, we describe here the design of a highly nuclease-resistant dimeric hairpin guanosine-quadruplex, [Gm3Um4Gm3-s], containing the 2'-O-methyl groups on the nucleoside and sulphur groups on the internucleotidic bonds, and its anti-HIV-1 activity in cultured cells. The unmodified and modified oligonucleotides were chemically synthesized. The anti-HIV activities of test compounds on HIV-1 infection were determined by protection against HIV-1-induced cytopathic effects. The mechanism of action of the oligonucleotides was determined by virus binding and detection [anti-CD4 monoclonal antibody (MAb) and anti-V3 MAb] assays. Gm3Um4Gm3-s was highly nuclease resistant, had significantly higher anti-HIV-1 activity than dG3T4G3-s, dG10-s and Gm10-s, and blocked the interaction between gp120 and CD4. The anti-HIV-1 activity of this oligonucleotide was increased when the phosphodiester and 2'-hydroxyl groups on the oligonucleotide backbones were replaced with a phosphorothioate and 2'-O-methyl backbone; thus Gm3Um4Gm3-s may inhibit HIV-1 infection, at least in part, by blocking the interaction between gp120 and CD4.

Independency of anti-HIV-1 activity from ribosome-inactivating activity of trichosanthin

Trichosanthin (TCS) is a type I ribosome-inactivating (RI) protein possessing multiple biological and pharmacological activities. Its major action is inhibition of human immunodeficiency virus (HIV) replication but the mechanism is still elusive. All evidences showed that this action is related to its RI activity. Previous studies found that TCS mutants with reduced RI activity simultaneously lost some anti-HIV activity. In this study, an exception was demonstrated by two TCS mutants retaining almost all RI activity but were devoid of anti-HIV-1 activity. Five mutants were constructed by using site-directed mutagenesis with either deletion or addition of amino acids to the C-terminal sequence. Results showed that the RI activity of mutants with C-terminal deletion mutants (TCS C2, TCS C4, and TCS C14) decreased by 1.2–3.3-fold with parallel downshifting of its anti-HIV-1 activity (1.4–4.8-fold). Another two mutants, TCS C19aa and TCS KDEL having 19 amino acid extension and a KDEL signal sequence added to the C-terminal sequence, retained all RI activity but subsequently lost most of the anti-HIV-1 activity. These findings suggested that ribosome inactivation alone might not be adequate to explain the anti-HIV action of TCS.

Lamivudine Can Exert a Modest Antiviral Effect against Human Immunodeficiency Virus Type 1 Containing the M184V Mutation

The M184V mutation in human immunodeficiency virus (HIV) reverse transcriptase is associated with high-level resistance to both (-)2',3'-dideoxy-3'-thiacytidine (3TC) and (-)2',3'-dideoxy-5-fluoro-3'-thiacytidine as well as low-level resistance to 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, and abacavir. This mutation is also associated with diminished HIV replicative fitness as well as several functional changes in enzyme activity, including diminutions in polymerase processivity, pyrophosphorylysis, and nucleotide primer unblocking. Despite the fact that M184V encodes up to 1,000-fold resistance to 3TC, we asked whether this drug might still display some antiviral effect in regard to viruses containing this mutation. Cell-free assays revealed that high concentrations of 3TC triphosphate (i.e., >100 micro M) could affect chain termination and/or inhibit purified reverse transcriptase containing the M184V substitution. This effect became more pronounced with elongation of reverse transcriptase products. In newly infected cells (i.e., peripheral blood mononuclear cells), we found that the amount of full-length reverse transcriptase product was diminished in the presence of 2 to 10 micro M 3TC, although no decrease in the first product of the reverse transcriptase reaction, i.e., minus strong-stop DNA, was observed. In the presence of two other HIV inhibitors, e.g., nevirapine and indinavir, 3TC exerted additive effects in tissue culture at concentrations only marginally higher than the 50% inhibitory concentration (IC(50)). Reverse transcriptases cloned from clinical isolates harboring M184V in the context of multidrug resistance had similar IC(50) values for 3TC triphosphate compared to reverse transcriptase containing only the M184V mutation. These results suggest that viruses containing M184V can retain a higher degree of sensitivity to 3TC than previously assumed.

Adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B: a review of the major clinical studies

Adefovir dipivoxil (ADF) is an orally bioavailable prodrug of adefovir, a phosphonate nucleotide analog of adenosine monophosphate [1]. Adefovir has potent in vitro activity against hepadnaviruses, retroviruses and herpesviruses [2–5]. The intracellular compound, adefovir diphosphate, acts as a competitive inhibitor and chain-terminator of hepatitis B virus (HBV) replication mediated by HBV DNA polymerase [6]. Ten mg daily of adefovir has recently been licensed for the treatment of chronic hepatitis B in adults with evidence of HBV replication. The efficacy of ADF was investigated in patients with compensated liver disease and evidence of HBV replication; in patients failing lamivudine therapy, including posttransplantation patients, patients with compensated and decompensated liver failure and patients co-infected with human immunodeficiency virus (HIV). Several of these studies have been published. The data in HBeAg-positive patients is reviewed in this manuscript.

Structure—Activity Relationships for the anti‐HIV Activity of Flavonoids.

Quantitative structure−activity relationship (QSAR) models are useful in providing a biochemical understanding of the biological activity of natural and synthetic chemicals based solely on molecular structure. One- to three-parameter multiregression equations were generated for three different groups of flavonoids to model experimental flavonoid-induced cytotoxicity and inhibition of human immunodeficiency virus I replication in lymphocyte-infected cells, using quantum chemical and geometrical parameters derived from optimized molecular structures. Both biological properties were basically dependent on electronic parameters describing charge distribution on the two fused rings of the flavonoid molecule. Atomic charges in C3 and the carbonyl carbon as well as the dipolar moment were important electronic descriptors to define the studied biological properties of flavonoids.

Inhibition of Cytopathic Effect of Human Immunodeficiency Virus Type‐1 by Various Phorbol Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.