Mode of Action of Zn-Complexes on Herpes Simplex Virus Type 1 Infection<i>In Vitro</i>

Varadinova, T.; Bontchev, P.R.; Nachev, C.; Shishkov, Stoyan; Strachilov, D.; Paskalev, Z.; Toutekova, A.; Panteva, M.

doi:10.1080/1120009x.1993.11739200

Cited by 19 publications

(8 citation statements)

References 8 publications

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“…We have found that when copper, zinc or cobalt is bound to a suitable ligand, the appropriate complex exibited a significant anti-HSV effect (Varadinova et al, 1993;1996). Recently published data by Sagripanti et al (1997) also show that the inhibition of HSV by copper was enhanced by reducing agents and that mechanism of the inactivation is similar as for coppermediated DNA damage (Aruoma, et al 1991;Dizdaroglu, et al, 1991;Toyokuni and Sagripanti, 1994).…”

Section: Discussionmentioning

confidence: 74%

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1and Type 2 (HSV‐1, HSV‐2) Infection in Cultured Cells

1998

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We have found that when copper, zinc or cobalt is bound to a suitable ligand, the appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996). Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by copper was enhanced by reducing agents and that mechanism of the inactivation is similar as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991; Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll) coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells. The experiments on cytotoxicity as well as on the activity of three different Cu-ACV complexes [Cu(ACV)2Cl2(H2O)2] = (A); [Cu(ACV)2(H2O)3](NO3)2.H2O = (B) and [Cu(ACV)2(H2O)2](NO3)2] = (C) towards virus replication, with special attention on the growth of ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference compound. The following results were obtained: 1) Increased cell’s viability in the presence of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative level (A) >> (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 (ACVR, TKa) - (A) > ACV > (C) > (B). This findings are consistent with previously published data and undoubtedly show that Cu-ACV complexes could be useful in the treatment of HSV infections, especially when the causative agent is a resistant to ACV mutant.

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Section: Discussionmentioning

confidence: 74%

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1and Type 2 (HSV‐1, HSV‐2) Infection in Cultured Cells

1998

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“…4, No. 1, 1997 Effect of Complexes of Zinc, Cobalt and Copper with D-Aminosugars on the Replication of Herpes Simplex v Virus Type 1 Zn(ll) with picolinic and with asp_artic acids are recommended (9).. In addition, the latter complexes.posses virucidal activity towards VZV virions, which is due to the virus-specific properties (11 ).…”

Section: Metal-based Drugsmentioning

confidence: 99%

Effect of Complexes of Zinc, Cobalt and Copper With D‐Aminosugars on the Replication of Herpes Simplex Virus Type 1 (HSV‐1)

Shishkov¹,

Varadinova²,

Panteva³

et al. 1996

Metal-Based Drugs

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Our previous results show that Zn(pic)2 and Zn(asp)2 inhibit key steps of the replication of HSV-1. Anti-HSV effect of complexes of Co(II) with aminoacids Lys and Ser was also found. In the present study we describe the effect of complexes of Zn(II), Co(II) and Cu(II) with D-aminosugars on the replication of HSV-1 and on the infectivity of free virions. The experiments were done using primary rabbit kidney cells (r.k.), diploid human embryonal fibroblasts (F) and Vero cells. No differences in the toxicity of metal complexes on diploid cells- r.k. and F, were found. Neither metal complexes, nor ligands-galactosoxime and glucosoxime, influenced the viral replication. During 1-4h prolonged contact only Cu(Gl.NOH)2 inactivated HSV-1 virions up to 90%. The results show that D-aminosugars are not suitable ligands for Zn(II), Cu(II) and Co(II) in respect of the inhibition of viral replication. However, only Cu(Gl.NOH)2 was able to inhibit the infectivity of free virions.

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“…Other agents used in therapy of VZV infection are Vidarabine and alpha-Interferon (9,10). Our previously published data have shown that Zn(pic) and Zn(asp)= inhibit key steps of H$Vreplication (11,12). However, the effect of these Zn-complexes on VZV infection in vitro is also of interest.…”

Section: Introductionmentioning

confidence: 87%

Complexes of Zinc With Picolinic and Aspartic Acids Inactivate Free Varicella‐Zoster Virions

et al. 1995

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Zn(ll) picolinate and aspartate, Zn(pic). and Zn(asp)., have been shown to inhibit key steps of the replication of HSV-I. In the present study we describe the effect of Zn(pic). and Zn(asp). on the replication of VZV and on the infectivity of free virions. The experiments are done using BHK-21 cells, a clinical isolate of VZV and Zn-complexes in concentration of 10/M. When Zn-complexes are present during the whole period of infection, the yield of infectious virus progeny decreases up to 98%. The infectivity of VZV is completely restored after the removal of zinc. The virucidal effect is manifested at the 2nd h of contact, when 90% of the virions are inactivated. The results show that both Zn(pic). and Zn(asp)= specifically inactivate free VZV virions with no effect on viral replication.

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Mode of Action of Zn-Complexes on Herpes Simplex Virus Type 1 InfectionIn Vitro

Cited by 19 publications

References 8 publications

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1and Type 2 (HSV‐1, HSV‐2) Infection in Cultured Cells

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1and Type 2 (HSV‐1, HSV‐2) Infection in Cultured Cells

Effect of Complexes of Zinc, Cobalt and Copper With D‐Aminosugars on the Replication of Herpes Simplex Virus Type 1 (HSV‐1)

Complexes of Zinc With Picolinic and Aspartic Acids Inactivate Free Varicella‐Zoster Virions

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