Valproic Acid and Its Amidic Derivatives As New Antivirals Against Alphaherpesviruses

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2020 Dec 1

PMID 33256172

Citations 13

Authors

Sabina Andreu

Ines Ripa

Raquel Bello-Morales

Jose Antonio Lopez-Guerrero

Affiliations

Soon will be listed here.

Abstract

Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.

Citing Articles

Transcriptome analysis of Burkitt lymphoma cells treated with anti-convulsant drugs that are inhibitors of Epstein-Barr virus lytic reactivation.

Gorres K, Reineke D, Miller G PLoS One. 2024; 19(4):e0299198.

PMID: 38635661 PMC: 11025866. DOI: 10.1371/journal.pone.0299198.

Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences.

Stakisaitis D, Kapocius L, Tatarunas V, Gecys D, Mickiene A, Tamosuitis T Pharmaceutics. 2024; 16(3).

PMID: 38543303 PMC: 10974540. DOI: 10.3390/pharmaceutics16030409.

Pseudorabies virus uses clathrin mediated endocytosis to enter PK15 swine cell line.

Andreu S, Agundez C, Ripa I, Lopez-Guerrero J, Bello-Morales R Front Microbiol. 2024; 15:1332175.

PMID: 38374920 PMC: 10876092. DOI: 10.3389/fmicb.2024.1332175.

Gene crosstalk between COVID-19 and preeclampsia revealed by blood transcriptome analysis.

Chu Y, Li M, Sun M, Wang J, Xin W, Xu L Front Immunol. 2024; 14:1243450.

PMID: 38259479 PMC: 10800816. DOI: 10.3389/fimmu.2023.1243450.

Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways.

Stakisaitis D, Kapocius L, Kilimaite E, Gecys D, Slekiene L, Balnyte I Pharmaceutics. 2023; 15(12).

PMID: 38140056 PMC: 10747708. DOI: 10.3390/pharmaceutics15122715.

References

Praena B, Bello-Morales R, de Castro F, Lopez-Guerrero J . Amidic derivatives of valproic acid, valpromide and valnoctamide, inhibit HSV-1 infection in oligodendrocytes. Antiviral Res. 2019; 168:91-99. DOI: 10.1016/j.antiviral.2019.05.006. View

Bialer M . Pharmacokinetic considerations in the design of better and safer new antiepileptic drugs. J Control Release. 1999; 62(1-2):187-92. DOI: 10.1016/s0168-3659(99)00037-1. View

Isoherranen N, Yagen B, Bialer M . New CNS-active drugs which are second-generation valproic acid: can they lead to the development of a magic bullet?. Curr Opin Neurol. 2003; 16(2):203-11. DOI: 10.1097/01.wco.0000063774.81810.30. View

Zanatta G, Sula A, Miles A, Ng L, Torella R, Pryde D . Valproic acid interactions with the NavMs voltage-gated sodium channel. Proc Natl Acad Sci U S A. 2019; 116(52):26549-26554. PMC: 6936711. DOI: 10.1073/pnas.1909696116. View

Bello-Morales R, Fedetz M, Alcina A, Tabares E, Lopez-Guerrero J . High susceptibility of a human oligodendroglial cell line to herpes simplex type 1 infection. J Neurovirol. 2005; 11(2):190-8. DOI: 10.1080/13550280590924179. View

Vere Hodge R, Field H . Antiviral agents for herpes simplex virus. Adv Pharmacol. 2013; 67:1-38. DOI: 10.1016/B978-0-12-405880-4.00001-9. View

Tomson T, Battino D, Perucca E . Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol. 2015; 15(2):210-218. DOI: 10.1016/S1474-4422(15)00314-2. View

Bialer M, Yagen B . Valproic Acid: second generation. Neurotherapeutics. 2007; 4(1):130-7. PMC: 7479693. DOI: 10.1016/j.nurt.2006.11.007. View

Lebrun-Vignes B . [Valaciclovir]. Ann Dermatol Venereol. 2002; 129(5 Pt 1):708-15. View

10.

Ornaghi S, Davis J, Gorres K, Miller G, Paidas M, van den Pol A . Mood stabilizers inhibit cytomegalovirus infection. Virology. 2016; 499:121-135. PMC: 5102808. DOI: 10.1016/j.virol.2016.09.012. View

11.

Widener R, Whitley R . Herpes simplex virus. Handb Clin Neurol. 2014; 123:251-63. DOI: 10.1016/B978-0-444-53488-0.00011-0. View

12.

Gorres K, Daigle D, Mohanram S, McInerney G, Lyons D, Miller G . Valpromide Inhibits Lytic Cycle Reactivation of Epstein-Barr Virus. mBio. 2016; 7(2):e00113. PMC: 4810481. DOI: 10.1128/mBio.00113-16. View

13.

Pires de Mello C, Bloom D, Paixao I . Herpes simplex virus type-1: replication, latency, reactivation and its antiviral targets. Antivir Ther. 2016; 21(4):277-86. DOI: 10.3851/IMP3018. View

14.

Bersudsky Y, Applebaum J, Gaiduk Y, Sharony L, Mishory A, Podberezsky A . Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double-blind, controlled, add-on clinical trial. Bipolar Disord. 2010; 12(4):376-82. DOI: 10.1111/j.1399-5618.2010.00828.x. View

15.

Piret J, Boivin G . Antiviral resistance in herpes simplex virus and varicella-zoster virus infections: diagnosis and management. Curr Opin Infect Dis. 2016; 29(6):654-662. DOI: 10.1097/QCO.0000000000000288. View

16.

Bollaerts K, Riera-Montes M, Heininger U, Hens N, Souverain A, Verstraeten T . A systematic review of varicella seroprevalence in European countries before universal childhood immunization: deriving incidence from seroprevalence data. Epidemiol Infect. 2017; 145(13):2666-2677. PMC: 5647669. DOI: 10.1017/S0950268817001546. View

17.

Anderson A, Gaffy C, Weseli J, Gorres K . Inhibition of Epstein-Barr Virus Lytic Reactivation by the Atypical Antipsychotic Drug Clozapine. Viruses. 2019; 11(5). PMC: 6563273. DOI: 10.3390/v11050450. View

18.

Al-Badr A, Ajarim T . Ganciclovir. Profiles Drug Subst Excip Relat Methodol. 2018; 43:1-208. DOI: 10.1016/bs.podrm.2017.12.001. View

19.

Vazquez-Calvo A, Saiz J, Sobrino F, Martin-Acebes M . Inhibition of enveloped virus infection of cultured cells by valproic acid. J Virol. 2010; 85(3):1267-74. PMC: 3020505. DOI: 10.1128/JVI.01717-10. View

20.

Johnston C, Gottlieb S, Wald A . Status of vaccine research and development of vaccines for herpes simplex virus. Vaccine. 2016; 34(26):2948-2952. DOI: 10.1016/j.vaccine.2015.12.076. View