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Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

El-Bitar AM, Sarhan MM, Aoki C, Takahara Y, Komoto M, Deng L, Moustafa MA, Hotta H - Virol. J. (2015)

Bottom Line: Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed.S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step.To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Faculty of Science, Al-Azhar University, Assiut, Egypt. sci.elbitar@gmail.com.

ABSTRACT

Background: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions.

Methods: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities.

Results: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV.

Conclusions: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

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Related in: MedlinePlus

Antiviral activity ofS. maurus palmatusvenom against dengue virus, measles virus and influenza virus. (A) Dengue virus and measles virus that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated as a control were inoculated to Vero/SLAM cells and cultivated for 24 hr. The number of virus-infected cells was determined by immunofluorescence and plaque assays and the percentages compared to the untreated control calculated. Data represent means ± SD of the data obtained from triplicate cultures. ‡, ~0.2% of the control. (B) Influenza virus and HCV that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated were inoculated to MDCK and Huh7.5 cells, respectively. The number of virus-infected cells was determined by immunofluorescence analysis and the percentages of the numbers of virus-infected cells compared to the untreated control calculated. Data represent means ± SEM of the data obtained from two independent experiments. *, P <0.05; †, P <0.001, compared with the untreated control. §, <0.01% of the control.
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Fig4: Antiviral activity ofS. maurus palmatusvenom against dengue virus, measles virus and influenza virus. (A) Dengue virus and measles virus that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated as a control were inoculated to Vero/SLAM cells and cultivated for 24 hr. The number of virus-infected cells was determined by immunofluorescence and plaque assays and the percentages compared to the untreated control calculated. Data represent means ± SD of the data obtained from triplicate cultures. ‡, ~0.2% of the control. (B) Influenza virus and HCV that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated were inoculated to MDCK and Huh7.5 cells, respectively. The number of virus-infected cells was determined by immunofluorescence analysis and the percentages of the numbers of virus-infected cells compared to the untreated control calculated. Data represent means ± SEM of the data obtained from two independent experiments. *, P <0.05; †, P <0.001, compared with the untreated control. §, <0.01% of the control.

Mentions: In order to determine whether or not the antiviral activity of S. maurus palmatus venom shown above was specific to HCV, we examined its possible effects on different viruses, such as dengue virus type 2 [35,36], measles virus [37] and influenza virus [38]. In this analysis, each virus was pre-treated with the venom (30 and 60 μg/ml) for 2 hr and the remaining virus infectivity was measured by infectious center or plaque assay. The result revealed that the venom exerted only weak inhibition on measles virus but strong inhibition on dengue virus (Figure 4A). Interestingly, the same venom did not inhibit but rather enhanced infectivity of influenza virus (Figure 4B).Figure 4


Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

El-Bitar AM, Sarhan MM, Aoki C, Takahara Y, Komoto M, Deng L, Moustafa MA, Hotta H - Virol. J. (2015)

Antiviral activity ofS. maurus palmatusvenom against dengue virus, measles virus and influenza virus. (A) Dengue virus and measles virus that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated as a control were inoculated to Vero/SLAM cells and cultivated for 24 hr. The number of virus-infected cells was determined by immunofluorescence and plaque assays and the percentages compared to the untreated control calculated. Data represent means ± SD of the data obtained from triplicate cultures. ‡, ~0.2% of the control. (B) Influenza virus and HCV that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated were inoculated to MDCK and Huh7.5 cells, respectively. The number of virus-infected cells was determined by immunofluorescence analysis and the percentages of the numbers of virus-infected cells compared to the untreated control calculated. Data represent means ± SEM of the data obtained from two independent experiments. *, P <0.05; †, P <0.001, compared with the untreated control. §, <0.01% of the control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374190&req=5

Fig4: Antiviral activity ofS. maurus palmatusvenom against dengue virus, measles virus and influenza virus. (A) Dengue virus and measles virus that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated as a control were inoculated to Vero/SLAM cells and cultivated for 24 hr. The number of virus-infected cells was determined by immunofluorescence and plaque assays and the percentages compared to the untreated control calculated. Data represent means ± SD of the data obtained from triplicate cultures. ‡, ~0.2% of the control. (B) Influenza virus and HCV that had been treated with S. maurus palmatus venom (30 and 60 μg/ml) for 2 hr or left untreated were inoculated to MDCK and Huh7.5 cells, respectively. The number of virus-infected cells was determined by immunofluorescence analysis and the percentages of the numbers of virus-infected cells compared to the untreated control calculated. Data represent means ± SEM of the data obtained from two independent experiments. *, P <0.05; †, P <0.001, compared with the untreated control. §, <0.01% of the control.
Mentions: In order to determine whether or not the antiviral activity of S. maurus palmatus venom shown above was specific to HCV, we examined its possible effects on different viruses, such as dengue virus type 2 [35,36], measles virus [37] and influenza virus [38]. In this analysis, each virus was pre-treated with the venom (30 and 60 μg/ml) for 2 hr and the remaining virus infectivity was measured by infectious center or plaque assay. The result revealed that the venom exerted only weak inhibition on measles virus but strong inhibition on dengue virus (Figure 4A). Interestingly, the same venom did not inhibit but rather enhanced infectivity of influenza virus (Figure 4B).Figure 4

Bottom Line: Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed.S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step.To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Faculty of Science, Al-Azhar University, Assiut, Egypt. sci.elbitar@gmail.com.

ABSTRACT

Background: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions.

Methods: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities.

Results: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV.

Conclusions: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

Show MeSH
Related in: MedlinePlus