Antimicrobial Peptide, LL-37, And Its Potential As An Anti-HIV Agent

2021 ◽  
Vol 44 (3) ◽  
pp. E64-71
Author(s):  
Ana Vera-Cruz ◽  
Nongnuj Tanphaichitr ◽  
Jonathan B. Angel
Keyword(s):  
Health Impact ◽  
High Rate ◽  
Limited Data ◽  
Inhibitory Effects ◽  
Hiv Replication ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus ◽  
Immunomodulatory Properties ◽  
Anti Hiv Agents ◽  
Anti Hiv

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted.

scholarly journals Novel Inhibitory Effects of γ-Glutamylcysteine Ethyl Ester against Human Immunodeficiency Virus Type 1 Production and Propagation

1998 ◽  
Vol 42 (5) ◽  
pp. 1200-1206 ◽  
Author(s):  
Satoshi Kubota ◽  
Shubhra Shetty ◽  
Huizhong Zhang ◽  
Shigehisa Kitahara ◽  
Roger J. Pomerantz
Keyword(s):  
Human Immunodeficiency Virus ◽  
Ethyl Ester ◽  
Human Immunodeficiency Virus Type ◽  
Inhibitory Effects ◽  
Immunodeficiency Virus ◽  
Acute Hiv ◽  
High Doses ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT The anti-human immunodeficiency virus type I (anti-HIV-1) effects of γ-glutamylcysteine ethyl ester (γ-GCE; TEI-2306) were examined in vitro. In initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line, γ-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection that was unlike that of other glutathione prodrugs or other reported antioxidants. In high doses, up to a concentration of 2.5 mM, at which neither glutathione (GSH) nor another GSH precursor has shown inhibitory effects, γ-GCE potently inhibited the production of HIV-1 by a selective cytopathic effect against infected cells, while the viability and growth of uninfected cells were unaffected at the same γ-GCE concentrations. At lower concentrations (200 to 400 μM), γ-GCE significantly repressed the virus production from chronically HIV-1-expressing cells without affecting their viability. The discrepancy of the thresholds of the toxic doses between infected and uninfected cells was found to be more than 10-fold. Relatively high doses of γ-GCE, utilized in acute HIV-1 infection of T-lymphocytic cells, entirely blocked the propagation of HIV-1 and rescued the cells from HIV-1-induced cell death. Furthermore, γ-GCE at such concentrations was found to directly inhibit the infectivity of HIV-1 within 4 h. Repressive effects of γ-GCE on acute HIV-1 infection in human primary human peripheral blood mononuclear cells were also demonstrated. Here, the anti-HIV-1 strategy utilizing γ-GCE is removal of both HIV-1-producing cells and free infectious HIV-1 in vitro, in place of specific immunoclearance in vivo, which might lead to an arrest or slowing of viral propagation in HIV-1-infected individuals.

Synthesis and Antiviral Activity of 1,3-Disubstituted Uracils against HIV-1 and HCMV

2003 ◽  
Vol 14 (5) ◽  
pp. 271-279 ◽  
Author(s):  
Tokumi Maruyama ◽  
Shigetada Kozai ◽  
Tetsuo Yamasaki ◽  
Myriam Witvrouw ◽  
Christophe Pannecouque ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Cytomegalovirus ◽  
Therapeutic Agents ◽  
Reverse Transcriptase Inhibitors ◽  
Uracil Derivatives ◽  
Immunodeficiency Virus ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Hiv 1

The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives. Therefore, we tried to prepare several 1,3-disubstituted uracils, which were easily obtainable from uracil by preparation under alkali and Mitsunobu conditions, and examined their antiviral activity against HIV-1 and human cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1-cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition against HCMV and HIV-1, respectively.

Syntheses of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 2-substituted-5-fluoroaniline: "cytosine replacement" analogs of deoxycytidine for evaluation as anticancer and antihuman immunodeficiency virus (anti-HIV) agents

2000 ◽  
Vol 78 (8) ◽  
pp. 1081-1088
Author(s):  
Zhi-Xian Wang ◽  
Leonard I Wiebe ◽  
Erik De Clercq ◽  
Jan Balzarini ◽  
Edward E Knaus
Keyword(s):  
Anticancer Agent ◽  
Coupling Reaction ◽  
Tumor Cell Lines ◽  
Immunodeficiency Virus ◽  
Sugar Ring ◽  
Type Coupling ◽  
Anti Hiv Agents ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

A group of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 5-fluoroaniline possessing a variety of aryl C-2 substituents (6a R = H, 6b R = F, 6c R = Me) were synthesized. Accordingly, a Heck-type coupling reaction of the 4-iodoaniline derivatives (13a–c) with the bis(tert-butyldimethylsilyl)glycal (11) in the presence of Pd(OAc)2 and Ph3As, followed by removal of the tert-butyldimethylsilyl protection groups using n-Bu4N+F-, yielded the corresponding 4-(β-D-glycero-pentofuran-3-ulos-1-yl)aniline derivatives (14a–c) having a C-3 C=O in the sugar ring. Reduction of the C-3 C=O compounds (14a–c) using NaB(OAc)3H afforded the target 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of the respective 2-substituted-5-fluoroaniline (6a–c). The deoxycytidine mimic, 3-fluoro-4-[1-(2-deoxy-β-D-ribofuranosyl)]aniline (6a), in which the cytosine ring of deoxycytidine is replaced by a 4-(3-fluoroaniline) ring system, was inactive as an anticancer agent against a variety of tumor cell lines, and as an antihuman immunodeficiency virus (HIV-1, HIV-2) agent. The failure of this unnatural deoxycytidine mimic (6a) to exhibit anticancer-antiviral activity may be due to its inability to undergo phosphorylation by host cell- and virus-induced kinases.Key words: fluoroanilines, deoxycytidine mimics, anticancer-antihuman immunodeficiency virus (HIV) evaluation.

scholarly journals Synthesis and Evaluation of Some Symmetrical Phosphate Dimer Derivatives of 3′-Modified Nucleosides as Potential anti-HIV Agents

1996 ◽  
Vol 7 (6) ◽  
pp. 330-337 ◽  
Author(s):  
C. McGuigan ◽  
H.-W. Tsang ◽  
N. Mahmood ◽  
A. J. Hay
Keyword(s):  
Human Immunodeficiency Virus ◽  
Analytical Data ◽  
Modified Nucleosides ◽  
Nucleoside Analogues ◽  
Immunodeficiency Virus ◽  
Anti Hiv Agents ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

Novel symmetrical nucIeotide-(5′,5′)-dimers of 3′-O-acetylthymidine, 3′-O-methylthymidine, 3′-O-ethylthymidine, 3′-O-n-propylthymidine and 3′-azido-3′-deoxythymidine (AZT) were synthesized as membrane soluble pro-drugs. These were prepared using phosphorodichloridate chemistry and were characterised by spectroscopic and analytical data. In-vitro evaluation of the derivatives in cells acutely infected with the human immunodeficiency virus (HIV-1) demonstrated a range of activities. These derivatives were generally found to display poor inhibition of HIV proliferation. Derivatives containing AZT moieties were found to be potent, but such compounds were less active than the parent nucleoside. The data indicated that the AZT-containing compounds act primarily via the release of the free nucleoside. However, in some cases, the dimers of certain inactive nucleoside analogues were found to be active. In these cases, release of the nucleoside alone cannot account for the activity.

TSAO-T Analogues Bearing Amino Acids at Position N-3 of Thymine: Synthesis and Anti-Human Immunodeficiency Virus Activity

2000 ◽  
Vol 11 (1) ◽  
pp. 61-69 ◽  
Author(s):  
C Chamorro ◽  
E De Clercq ◽  
J Balzarini ◽  
M-J Camarasa ◽  
A San-Félix
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Effect ◽  
Acid Moiety ◽  
Hiv Replication ◽  
Virus Activity ◽  
Immunodeficiency Virus ◽  
Amino Acid Moiety ◽  
Anti Hiv ◽  
Hiv 1

Novel analogues of the anti-HIV-1 lead compound [1-[2‘,5’-bis- O-( tert-butyldimethylsilyl)-β-D-ribofuranosyl]thymine]-3‘-spiro-5’-(4“-amino-1”,2“-oxathiole-2‘,2’-dioxide) (TSAO-T) bearing different amino acids at position N-3 of thymine were prepared and evaluated as inhibitors of HIV replication. The synthesis of the target compounds was accomplished by coupling of the appropriate TSAO intermediate with a conveniently protected (L) amino acid in the presence of BOP and triethylamine, followed by depro-tection of the amino acid moiety. Several TSAO derivatives, bearing at N-3 position of the thymine base an L-amino acid retaining the free carboxylic acid, acquired activity against HIV-2, in addition to their inhibitory effect on HIV-1.

scholarly journals Sensitivity of human immunodeficiency virus infection to various α, β and γ chemokines

1999 ◽  
Vol 80 (9) ◽  
pp. 2369-2373 ◽  
Author(s):  
Giampaolo Greco ◽  
Carl Mackewicz ◽  
Jay A. Levy
Keyword(s):  
Cell Culture ◽  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Therapeutic Strategies ◽  
Hiv Replication ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Large Panel ◽  
High Concentrations ◽  
Anti Hiv

Examination of a large panel of chemokines indicates that in addition to RANTES, MIP-1α and MIP-1β, the β-chemokine MCP-2 and, to a lesser extent, the γ-chemokine lymphotactin also show anti-human immunodeficiency virus (HIV) activity in cell culture. The amount of chemokine needed to suppress HIV replication by ≤50% was generally greater (≤250 ng/ml) than that required for inhibition of virus infection by RANTES, MIP-1α and MIP-1β. The β-chemokine MCP-3 was found to enhance the replication of both non-syncytium-inducing (NSI) and syncytium-inducing (SI) viruses at high concentrations (0·5–5 μg/ml). In contrast to a previous report, macrophage-derived chemokine was not found to inhibit HIV replication of either NSI or SI viruses, but at low concentrations enhanced NSI virus replication. When small amounts of RANTES or MCP-2 were added together with high concentrations of non-inhibitory chemokines, the anti-HIV effects were countered. Information on chemokines that affect HIV infection could be useful for future therapeutic strategies.

Effects of bone marrow stimulatory cytokines on human immunodeficiency virus replication and the antiviral activity of dideoxynucleosides in cultures of monocyte/macrophages

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 995-1003 ◽  
Author(s):  
CF Perno ◽  
DA Cooney ◽  
WY Gao ◽  
Z Hao ◽  
DG Johns ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Human Immunodeficiency Virus ◽  
Human Peripheral Blood ◽  
Peripheral Blood Monocyte ◽  
Human Immunodeficiency Virus Replication ◽  
Hiv Replication ◽  
Gm Csf ◽  
Immunodeficiency Virus ◽  
Human Peripheral Blood Monocyte ◽  
Anti Hiv

Abstract Cells of the monocyte lineage are important targets for the replication of human immunodeficiency virus (HIV). Our group and others have previously shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates HIV replication in monocyte/macrophages, but that it also enhances the anti-HIV activity of 2′,3′-dideoxy-3′- azidothymidine (AZT). In the present study, we have explored the effects of other bone marrow stimulatory cytokines on the replication of HIV and on the anti-HIV activity of certain dideoxynucleosides in human peripheral blood monocyte/macrophages (M/M). Like GM-CSF, macrophage CSF (M-CSF) enhanced HIV replication in M/M. In contrast, granulocyte CSF (G-CSF) and erythropoietin (Epo) had no such effects. The anti-HIV activity of zidovudine (AZT) was increased in M/M exposed to GM-CSF. In contrast, the anti-HIV activity of AZT was unchanged in M/M exposed to M-CSF, and the activities of 2′,3′-dideoxycytidine (ddC) and 2′,3′-dideoxyinosine (ddl) were unchanged or slightly diminished in M/M stimulated with GM-CSF or M-CSF. These differential activities of AZT and ddC were paralleled by differential effects of the cytokines on the anabolism of these drugs to their active 5′-triphosphate moieties. GM-CSF increased the levels of AZT-5′-triphosphate (at least in part through an increase in thymidine kinase activity) and overall induced an increase in the ratio of AZT-5′-triphosphate/thymidine-5′- triphosphate. In contrast, M-CSF-induced increases in AZT-5′- triphosphate were roughly matched by increases in thymidine-5′- triphosphate. Also, GM-CSF- or M-CSF-induced increases in the levels of ddC-5′-triphosphate were associated with parallel increases in the levels of deoxycytidine-5′-triphosphate (the physiologic nucleoside that competes at the level of reverse transcriptase), so that there was relatively little net change in the ddC-5′-triphosphate/deoxycytidine- 5′-triphosphate ratio. Thus, bone marrow stimulatory cytokines may have a variety of effects on HIV replication and on the activity and metabolism of dideoxynucleosides in M/M.

scholarly journals Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal Complexes of 4-Hydroxycoumarins in Cell Culture

2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Ilia Manolov ◽  
Sevda Raleva ◽  
Petya Genova ◽  
Alexey Savov ◽  
Liliana Froloshka ◽  
...  
Keyword(s):  
Viral Replication ◽  
Earth Metal ◽  
H Nmr ◽  
Immunodeficiency Virus ◽  
Physicochemical Methods ◽  
Anti Hiv Agents ◽  
First Time ◽  
Anti Hiv ◽  
Hiv 1

The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3′-benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection. The complexes were characterized by different physicochemical methods: mass spectrometry, ¹H NMR, ¹³C NMR, and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2 cells by microtiter infection assay. Detection of endogenous reverse transcriptase (RT) activity and RT processivity by PCR indicative for proviral DNA synthesis demonstrated that anti-HIV activity has not been linked to early stages of viral replication. No effect on late steps of viral replication has been found using cells chronically producing HIV-1LAIvirus. La(W) demonstrated anti-HIV activity (IC50=21.4μM) close to maximal nontoxic concentration. Nd(W), Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by La(W) is under progress.

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