Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus
Introduction: Thousands of human infective viruses spread worldwide, yet protective measures exist for only a fraction, with internationally accepted vaccines available for an even smaller subset. Treatment options are limited, often restricted to symptom management, as specific antiviral agents rem...
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Elsevier
2025-03-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S120197122400568X |
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| author | Ms Krisztina Leiner Mr Valentin Molnár Mr Zoltán Kopasz Mrs Ilona Bakai-Bereczki Ms Eszter Lőrincz Dr. Eszter Szabó Dr. Mónika Madai Dr. Anikó Borbás Dr. Anett Kuczmog |
| author_facet | Ms Krisztina Leiner Mr Valentin Molnár Mr Zoltán Kopasz Mrs Ilona Bakai-Bereczki Ms Eszter Lőrincz Dr. Eszter Szabó Dr. Mónika Madai Dr. Anikó Borbás Dr. Anett Kuczmog |
| author_sort | Ms Krisztina Leiner |
| collection | DOAJ |
| description | Introduction: Thousands of human infective viruses spread worldwide, yet protective measures exist for only a fraction, with internationally accepted vaccines available for an even smaller subset. Treatment options are limited, often restricted to symptom management, as specific antiviral agents remain elusive for most viruses, including the Sindbis virus. Originating in Africa, Sindbis virus, a member of the Alphavirus genus, is primarily transmitted by arthropod vectors, notably mosquitoes, leading to the manifestation of Sindbis fever characterized by symptoms including rash, headache, joint pain, and fatigue, highlighting its significance as a vector-borne human pathogen. While historically associated with major epidemics in northern European countries such as Ockelbo and Pogosta disease, and Karelian fever, the virus's potential for global spread necessitates vigilance and preparedness for the emergence of outbreaks in new regions. In this context, the exploration of repurposed therapeutics, such as derivatives of glycopeptide antibiotics, holds promise for combating Sindbis virus and other viral pathogens, given their observed antiviral activity against a spectrum of viruses including influenza, Dengue virus, West-Nile virus and Human Immundeficiency virus. Methods: We investigated the antiviral efficacy of 26 synthetic antibiotics and derivatives against Sindbis virus in vitro, using Vero E6 cells. Initial compounds included teicoplanin, ristocetin, and vancomycin and their derivatives. Cytotoxicity assessment preceded evaluation of antiviral potential via microscopic analysis, MTT assay, and quantitative PCR analysis to measure changes in viral copy numbers. Results: Four compounds exhibited potent inhibitory effects, with two demonstrating moderate antiviral activity. Among them, a ristocetine derivative (ERJ-552) displayed exceptional potency against Sindbis virus. Further investigations into its mechanism of action were conducted using a time addition assay to determine its antiviral effects during the infection cycle. Discussion: Our findings underscore the potential of repurposed antibiotics and their derivatives in combating Sindbis virus. The identification of ERJ-552 as a potent antiviral compound highlights avenues for further research into novel therapeutics against alphaviruses and other viral pathogens. The study elucidates the importance of exploring existing drugs for new applications in viral therapy. Conclusion: In conclusion, our study demonstrates the antiviral efficacy of synthetic antibiotics and derivatives against Sindbis virus, with ERJ-552 emerging as a particularly promising candidate. These findings contribute to the ongoing efforts to develop effective treatments against emerging viral pathogens, emphasizing the significance of repurposing existing drugs in the fight against infectious diseases. |
| format | Article |
| id | doaj-art-af902bf90d0d4ff283d67a382cf74d69 |
| institution | OA Journals |
| issn | 1201-9712 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj-art-af902bf90d0d4ff283d67a382cf74d692025-08-20T02:00:41ZengElsevierInternational Journal of Infectious Diseases1201-97122025-03-0115210749310.1016/j.ijid.2024.107493Antiviral activity of glycopeptide antibiotics derivates against Sindbis virusMs Krisztina Leiner0Mr Valentin Molnár1Mr Zoltán Kopasz2Mrs Ilona Bakai-Bereczki3Ms Eszter Lőrincz4Dr. Eszter Szabó5Dr. Mónika Madai6Dr. Anikó Borbás7Dr. Anett Kuczmog8National Laboratory Of Virology, Szentágothai Research Centre; Institute of Biology, Faculty of Sciences, University of PécsUniversity of Pécs Medical SchoolNational Laboratory Of Virology, Szentágothai Research Centre; Institute of Biology, Faculty of Sciences, University of PécsDepartment of Pharmaceutical Chemistry, University of Debrecen; National Research, Development and Innovation Office of HungaryDepartment of Pharmaceutical Chemistry, University of DebrecenNational Laboratory Of Virology, Szentágothai Research CentreNational Laboratory Of Virology, Szentágothai Research CentreDepartment of Pharmaceutical Chemistry, University of DebrecenNational Laboratory Of Virology, Szentágothai Research Centre; Institute of Biology, Faculty of Sciences, University of PécsIntroduction: Thousands of human infective viruses spread worldwide, yet protective measures exist for only a fraction, with internationally accepted vaccines available for an even smaller subset. Treatment options are limited, often restricted to symptom management, as specific antiviral agents remain elusive for most viruses, including the Sindbis virus. Originating in Africa, Sindbis virus, a member of the Alphavirus genus, is primarily transmitted by arthropod vectors, notably mosquitoes, leading to the manifestation of Sindbis fever characterized by symptoms including rash, headache, joint pain, and fatigue, highlighting its significance as a vector-borne human pathogen. While historically associated with major epidemics in northern European countries such as Ockelbo and Pogosta disease, and Karelian fever, the virus's potential for global spread necessitates vigilance and preparedness for the emergence of outbreaks in new regions. In this context, the exploration of repurposed therapeutics, such as derivatives of glycopeptide antibiotics, holds promise for combating Sindbis virus and other viral pathogens, given their observed antiviral activity against a spectrum of viruses including influenza, Dengue virus, West-Nile virus and Human Immundeficiency virus. Methods: We investigated the antiviral efficacy of 26 synthetic antibiotics and derivatives against Sindbis virus in vitro, using Vero E6 cells. Initial compounds included teicoplanin, ristocetin, and vancomycin and their derivatives. Cytotoxicity assessment preceded evaluation of antiviral potential via microscopic analysis, MTT assay, and quantitative PCR analysis to measure changes in viral copy numbers. Results: Four compounds exhibited potent inhibitory effects, with two demonstrating moderate antiviral activity. Among them, a ristocetine derivative (ERJ-552) displayed exceptional potency against Sindbis virus. Further investigations into its mechanism of action were conducted using a time addition assay to determine its antiviral effects during the infection cycle. Discussion: Our findings underscore the potential of repurposed antibiotics and their derivatives in combating Sindbis virus. The identification of ERJ-552 as a potent antiviral compound highlights avenues for further research into novel therapeutics against alphaviruses and other viral pathogens. The study elucidates the importance of exploring existing drugs for new applications in viral therapy. Conclusion: In conclusion, our study demonstrates the antiviral efficacy of synthetic antibiotics and derivatives against Sindbis virus, with ERJ-552 emerging as a particularly promising candidate. These findings contribute to the ongoing efforts to develop effective treatments against emerging viral pathogens, emphasizing the significance of repurposing existing drugs in the fight against infectious diseases.http://www.sciencedirect.com/science/article/pii/S120197122400568X |
| spellingShingle | Ms Krisztina Leiner Mr Valentin Molnár Mr Zoltán Kopasz Mrs Ilona Bakai-Bereczki Ms Eszter Lőrincz Dr. Eszter Szabó Dr. Mónika Madai Dr. Anikó Borbás Dr. Anett Kuczmog Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus International Journal of Infectious Diseases |
| title | Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus |
| title_full | Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus |
| title_fullStr | Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus |
| title_full_unstemmed | Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus |
| title_short | Antiviral activity of glycopeptide antibiotics derivates against Sindbis virus |
| title_sort | antiviral activity of glycopeptide antibiotics derivates against sindbis virus |
| url | http://www.sciencedirect.com/science/article/pii/S120197122400568X |
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