Inhibition of HIV-1 infection by zinc group metal compounds

Haraguchi, Yuji; Sakurai, Hiromu; Hussain, Saver; Anner, Béatrice M.; Hoshino, Hiroo

doi:10.1016/s0166-3542(99)00040-6

Cited by 93 publications

(72 citation statements)

References 17 publications

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“…Alternatively, zinc may block the protease activity in rhinovirus, thereby preventing the breakdown of the virus polypeptide necessary to generate individual functional proteins. Zinc compounds owe their anti-HIV-1 effects to inhibition of HIV-1 DNA-to-RNA transcription, rather than inhibition of the adsorption or penetration, contrary to our observation on RSV in this study (10).…”

contrasting

confidence: 99%

“…However, complete inhibition was observed at a concentration 50 to 5,000 times higher than observed in our study. Zinc compounds at 100 g/ml inhibited HIV infection in vitro (10), though an effect on HIV syncytium formation was not observed at this concentration. This finding is in contrast to our observation, i.e., that zinc not only inhibited RSV replication but also prevented plaque formation, even when added in the semisolid overlay media only after virus infection of the cell monolayer.…”

Section: Discussionmentioning

confidence: 78%

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Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Suara¹,

Crowe

2004

Antimicrob Agents Chemother

132

123

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Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 M. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were >10 6 -fold. At the lowest concentration tested, 10 M, we observed >1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.Respiratory syncytial virus (RSV) is the most important viral cause of acute respiratory tract infection (ARI) in infancy and early childhood, with its greatest morbidity in infants (6,8,9). Throughout the world, RSV contributes significantly to annual hospital admissions due to ARI, especially during the epidemic season (18,23,27). In developing countries, malnutrition and deficiencies of micronutrients are associated with increased incidence and severity of ARI (25). Improvement in nutritional status might be a practical strategy for prevention of severe RSV disease in developing countries, if efficacious. At this time, however, we have a poor understanding of the role of micronutrients such as zinc in susceptibility to severe disease caused by RSV infection.Zinc supplementation in children in developing countries was demonstrated to cause a significant reduction in the prevalence of pneumonia (3,20). Zinc has been shown to mediate antiviral effects against certain viruses. Clinical studies showed that zinc significantly shortens the duration of symptoms during rhinovirus infection (17,19,28). Topical application of zinc sulfate also was found in one study to be effective in the treatment of herpes simplex virus (HSV) infection (26). The specific mechanism by which zinc mediated these clinical effects is unknown in most cases. Zinc also enhances the host response to ma...

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contrasting

confidence: 99%

Section: Discussionmentioning

confidence: 78%

Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Suara¹,

Crowe

2004

Antimicrob Agents Chemother

132

123

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“…Zinc salts have been shown to have in vitro activity against a variety of pathogens, including the causative agents of a number of important sexually transmitted diseases (STD), such as human immunodeficiency virus, herpes simplex virus (HSV), and Chlamydia trachomatis (1,9,11,12,14,17,18). In addition to in vitro activity, mice inoculated intravaginally with HSV type 2 (HSV-2) and then treated either with 100 mM zincmedicated collagen sponges or by an intravaginal 100 mM zinc salt douche had reduced incidences of genital herpes compared to controls (19,20).…”

mentioning

confidence: 99%

Efficacy and Toxicity of Zinc Salts as Candidate Topical Microbicides against Vaginal Herpes Simplex Virus Type 2 Infection

Bourne

Stegall

Montano

et al. 2005

Antimicrob Agents Chemother

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Zinc salt solutions administered as topical microbicides provided significant protection against herpes simplex virus type 2 infection in a mouse vaginal challenge model. However, at the therapeutic concentration, the salt solutions caused sloughing of sheets of vaginal epithelial cells. These observations limit the utility of zinc salts as microbicides and suggest that the application of zinc solutions to mucosal surfaces has the potential to cause damage that might increase susceptibility to secondary infections at a later time.

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“…Zinc has been studied for its antiviral effect in HIV, rhinovirus, and herpes virus [11][12][13][14]. In addition to its antiinflammatory effect, zinc exerts an antioxidant effect and induces metallothionein (MT), which has radical scavenging and immunomodulatory properties [12,15].…”

Section: Discussionmentioning

confidence: 99%

Blood cell, liver function, and response changes by PEG-interferon-α2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C

Kim

Sasase

et al. 2008

Hepatol Int

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Purpose Zinc has been reported to ameliorate hematologic side effects and improve liver function. In addition to its various effects, zinc supplementation in chronic hepatitis C patients with genotype 1b of high viral load enhanced the response to interferon (IFN) monotherapy. This study was aimed at clarifying whether zinc could improve hematologic side effects, improve liver function, and enhance the response to therapy in patients with chronic hepatitis C treated with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). Methods The 32 patients enrolled in the study were randomly divided into two groups: a PEG-IFN-a2b plus RBV with zinc group (PEG/RBV + zinc, n = 16) and a PEG-IFN-a2b plus RBV group (PEG/RBV, n = 16). HCV-RNA, serum zinc, ALT, white blood cell, red blood cell, platelet, and hemoglobin (Hb) levels were examined. Results Serum zinc levels were significantly higher in the PEG/RBV with zinc group than in the PEG/RBV without zinc group at 4, 8, and 12 weeks. No significant differences were observed in the clearance of HCV-RNA between the two groups. The outcome of the treatment was similar; results of laboratory examinations including ALT before, during, and after therapy revealed no significant differences between the two groups at any point in all items except serum zinc levels. A sustained virological response rate was observed in 50.0% in the PEG/RBV with zinc group and 43.8% in the PEG/RBV without zinc group, with no significant difference between the two groups. Conclusions The study demonstrated no evidence that zinc ameliorates hematologic side effects, improves liver function, and enhances the response to the therapy in chronic hepatitis C receiving PEG-IFN-a2b plus RBV.

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Inhibition of HIV-1 infection by zinc group metal compounds

Cited by 93 publications

References 17 publications

Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Efficacy and Toxicity of Zinc Salts as Candidate Topical Microbicides against Vaginal Herpes Simplex Virus Type 2 Infection

Blood cell, liver function, and response changes by PEG-interferon-α2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C

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