Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom
Herpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a chal...
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2024-02-01
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author | Pichet Praphawilai Thida Kaewkod Sureeporn Suriyaprom Aussara Panya Terd Disayathanoowat Yingmanee Tragoolpua |
author_facet | Pichet Praphawilai Thida Kaewkod Sureeporn Suriyaprom Aussara Panya Terd Disayathanoowat Yingmanee Tragoolpua |
author_sort | Pichet Praphawilai |
collection | DOAJ |
description | Herpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a challenge. Thus, the search for new antiviral and anti-inflammatory agents is a necessity. Melittin is a major peptide that is present in the venom of the honeybee. It possesses a number of pharmacological properties. In this study, the effects of the melittin peptides from <i>A. mellifera</i> (MEL-AM) and <i>A. florea</i> (MEL-AF) against HSV-1 and HSV-2 were evaluated at different stages during the viral multiplication cycle in an attempt to define the mode of antiviral action using plaque reduction and virucidal assays. The results revealed a new finding that melittin at 5 µg/mL demonstrated the highest inhibitory effect on HSV through the direct inactivation of viral particles, and MEL-AF displayed a greater virucidal activity. Moreover, melittin was also observed to interfere with the process of HSV attachment to the host cells. MEL-AM exhibited anti-HSV-1 and anti-HSV-2 effects with EC<sub>50</sub> values of 4.90 ± 0.15 and 4.39 ± 0.20 µg/mL, while MEL-AF demonstrated EC<sub>50</sub> values of 4.47 ± 0.21 and 3.95 ± 0.61 µg/mL against HSV-1 and HSV-2, respectively. However, non-cytotoxic concentrations of both types of melittin produced only slight degrees of HSV-1 and HSV-2 inhibition after viral attachment, but melittin at 5 µg/mL was able to reduce the plaque size of HSV-2 when compared to the untreated group. In addition, MEL-AM and MEL-AF also exhibited anti-inflammatory activity via the inhibition of nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells, and they were also found to down-regulate the expressions of the <i>iNOS</i>, <i>COX-2</i> and <i>IL-6</i> genes. The highest inhibition of <i>IL-6</i> mRNA expression was found after treatment with 10 µg/mL of MEL-AM and MEL-AF. Therefore, melittin peptides have displayed strong potential to be used as an alternative treatment for HSV infection and inflammatory diseases in the future. |
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spelling | doaj.art-eb20a6344bba4015a56f4635b37039cd2024-02-23T15:21:31ZengMDPI AGInsects2075-44502024-02-0115210910.3390/insects15020109Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> VenomPichet Praphawilai0Thida Kaewkod1Sureeporn Suriyaprom2Aussara Panya3Terd Disayathanoowat4Yingmanee Tragoolpua5Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandHerpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a challenge. Thus, the search for new antiviral and anti-inflammatory agents is a necessity. Melittin is a major peptide that is present in the venom of the honeybee. It possesses a number of pharmacological properties. In this study, the effects of the melittin peptides from <i>A. mellifera</i> (MEL-AM) and <i>A. florea</i> (MEL-AF) against HSV-1 and HSV-2 were evaluated at different stages during the viral multiplication cycle in an attempt to define the mode of antiviral action using plaque reduction and virucidal assays. The results revealed a new finding that melittin at 5 µg/mL demonstrated the highest inhibitory effect on HSV through the direct inactivation of viral particles, and MEL-AF displayed a greater virucidal activity. Moreover, melittin was also observed to interfere with the process of HSV attachment to the host cells. MEL-AM exhibited anti-HSV-1 and anti-HSV-2 effects with EC<sub>50</sub> values of 4.90 ± 0.15 and 4.39 ± 0.20 µg/mL, while MEL-AF demonstrated EC<sub>50</sub> values of 4.47 ± 0.21 and 3.95 ± 0.61 µg/mL against HSV-1 and HSV-2, respectively. However, non-cytotoxic concentrations of both types of melittin produced only slight degrees of HSV-1 and HSV-2 inhibition after viral attachment, but melittin at 5 µg/mL was able to reduce the plaque size of HSV-2 when compared to the untreated group. In addition, MEL-AM and MEL-AF also exhibited anti-inflammatory activity via the inhibition of nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells, and they were also found to down-regulate the expressions of the <i>iNOS</i>, <i>COX-2</i> and <i>IL-6</i> genes. The highest inhibition of <i>IL-6</i> mRNA expression was found after treatment with 10 µg/mL of MEL-AM and MEL-AF. Therefore, melittin peptides have displayed strong potential to be used as an alternative treatment for HSV infection and inflammatory diseases in the future.https://www.mdpi.com/2075-4450/15/2/109anti-herpes simplex virusanti-inflammationbee venomherpes simplex virusmelittinplaque reduction assay |
spellingShingle | Pichet Praphawilai Thida Kaewkod Sureeporn Suriyaprom Aussara Panya Terd Disayathanoowat Yingmanee Tragoolpua Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom Insects anti-herpes simplex virus anti-inflammation bee venom herpes simplex virus melittin plaque reduction assay |
title | Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom |
title_full | Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom |
title_fullStr | Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom |
title_full_unstemmed | Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom |
title_short | Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from <i>Apis mellifera</i> and <i>Apis florea</i> Venom |
title_sort | anti herpes simplex virus and anti inflammatory activities of the melittin peptides derived from i apis mellifera i and i apis florea i venom |
topic | anti-herpes simplex virus anti-inflammation bee venom herpes simplex virus melittin plaque reduction assay |
url | https://www.mdpi.com/2075-4450/15/2/109 |
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