Investigation of β-Carboline Alkaloid Harmaline Against Cyvirus cyprinidallo3 Infection In Vitro and In Vivo.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Harmaline*/pharmacology ; Antiviral Agents*/pharmacology ; Fish Diseases*/virology ; Fish Diseases*/drug therapy ; Herpesviridae Infections*/drug therapy ; Herpesviridae Infections*/veterinary ; Herpesviridae Infections*/virology ; Herpesviridae*/drug effects ; Herpesviridae*/physiology; Animals ; Carps/virology ; Virus Latency/drug effects ; Harmine/pharmacology ; Cell Line ; Carbolines/pharmacology ; Virus Activation/drug effects ; Virus Replication/drug effects

Cyvirus cyprinidallo3 , also known as Cyprinid herpesvirus 3 (CyHV-3), is a common pathogen of koi and common carp ( Cyprinus carpio ). Infection of CyHV-3 can lead to high mortality in fry under 4 months of age. CyHV-3 can become latent in recovered fish, and latent CyHV-3 can reactivate under stress conditions and spread the virus. Reactivation of CyHV-3 can also lead to mortality and diseases in latently infected fish. No effective drugs are available to prevent CyHV-3 infection or reactivation from latency. There is a need for the discovery of anti-CyHV-3 drugs. Harmine (HAR) and harmaline (HAL) are β-carboline alkaloids found in the medicinal plant Peganum harmala with antiviral activities against many viruses, including HSV. Here, HAL was evaluated against CyHV-3 infection in vitro and in vivo, respectively. Immediately after a one-hour infection exposure of ~1000 FPU/plate or ~500 PFU/plate, cells treated with 5 µM HAL for 2 h can block nearly 50% or 90% plaque formation in vitro. Only around 50% inhibition was observed in cells treated with the common anti-herpesvirus drug acyclovir (ACV) at 10 or 20 µM for 2 h following 1 h post-infection of ~500 PFU/plate. Cells treated with 10 µM HAL for 30 min, 60 min, 2 h, and 6 h can reduce 60%, 65%, 85.5%, and 85% CyHV-3 replication in vitro, respectively. HAL at 20 µM is still effective against CyHV-3 DNA replication and virion production when the treatment started at 3 and 5 days post-infection for 1 or 2 h, respectively. HAL under 50 µM has little toxicity to cells treated for 24 h. Immersion treatment with 10 µM HAL for 3-4 h daily within the first 5 days post-infection can increase the survival of fry by 60%. In addition, IM injection of HAL at 20 µM can reduce the rate of CyHV-3 reactivation induced by heat stress in latently infected koi. This study demonstrated that HAL could potentially be used to prevent CyHV-3 infection or reactivation from latency.

Biomed Res Int. 2018 Jan 15;2018:4810394. (PMID: 29568754)
J Virol. 2023 Mar 30;97(3):e0198422. (PMID: 36877059)
Vet Microbiol. 2009 Mar 30;135(3-4):261-6. (PMID: 19013729)
Vaccine. 2008 Jul 4;26(29-30):3750-6. (PMID: 18534721)
Dis Aquat Organ. 2005 Nov 9;67(1-2):15-23. (PMID: 16385803)
Cytotechnology. 1992;8(3):231-6. (PMID: 1368820)
Front Vet Sci. 2020 Oct 22;7:587952. (PMID: 33195621)
Virus Res. 2017 Aug 15;240:200-206. (PMID: 28860099)
Int J Mol Sci. 2024 May 02;25(9):. (PMID: 38732185)
Fish Shellfish Immunol. 2019 Oct;93:531-541. (PMID: 31369858)
Antiviral Res. 2015 Nov;123:27-38. (PMID: 26348003)
J Virol Methods. 2011 Mar;172(1-2):81-4. (PMID: 21185329)
Dis Aquat Organ. 2002 Mar 11;48(2):101-8. (PMID: 12005231)
J Fish Dis. 2009 Apr;32(4):311-20. (PMID: 19236553)
Am J Vet Res. 2000 Oct;61(10):1232-40. (PMID: 11039553)
Appl Environ Microbiol. 2009 Nov;75(21):6900-4. (PMID: 19734343)
J Virol. 2011 May;85(10):4954-62. (PMID: 21389134)
J Gen Virol. 2005 Jun;86(Pt 6):1659-1667. (PMID: 15914843)
Front Microbiol. 2023 Jan 13;13:1111930. (PMID: 36713204)
Dis Aquat Organ. 2004 Sep 8;60(3):179-87. (PMID: 15521316)
Biochem Biophys Res Commun. 1968 May 10;31(3):488-94. (PMID: 4968234)
J Fish Dis. 2011 Jul;34(7):547-54. (PMID: 21675996)
Microb Pathog. 2018 Jan;114:291-298. (PMID: 29223449)
J Virol Methods. 2013 Feb;187(2):372-9. (PMID: 23174162)
Sci Rep. 2023 Jan 28;13(1):1612. (PMID: 36709362)
Antiviral Res. 2016 Oct;134:26-33. (PMID: 27568370)
J Fish Dis. 2018 Nov;41(11):1709-1718. (PMID: 30144085)
J Neurovirol. 2007 Oct;13(5):416-25. (PMID: 17994426)
J Virol. 2023 Oct 31;97(10):e0039623. (PMID: 37706687)
Fish Shellfish Immunol. 2019 Feb;85:90-98. (PMID: 29567141)
J Virol. 2014 Aug;88(16):9297-309. (PMID: 24899202)
Vet Res. 2016 Mar 22;47:47. (PMID: 27000063)
Arch Pharm Res. 2020 Dec;43(12):1259-1275. (PMID: 33206346)
J Vet Res. 2019 Oct 24;63(4):513-518. (PMID: 31934661)
Front Pharmacol. 2018 Apr 10;9:346. (PMID: 29755345)
Viruses. 2023 Jan 05;15(1):. (PMID: 36680202)
Int J Mol Sci. 2023 Feb 28;24(5):. (PMID: 36902102)
Drug Test Anal. 2017 May;9(5):754-768. (PMID: 27377954)
Photochem Photobiol. 1986 Jan;43(1):21-6. (PMID: 3006095)
Dis Aquat Organ. 2004 Oct 21;61(1-2):165-8. (PMID: 15584424)
J Aquat Anim Health. 2000 Mar;12(1):44-57. (PMID: 28880775)
Int Immunopharmacol. 2018 Jul;60:111-120. (PMID: 29730555)
Virusdisease. 2018 Dec;29(4):445-452. (PMID: 30539046)

Keywords: CyHV-3; acyclovir; harmaline; reactivation; temperature stress

CN58I4TOET (Harmaline)
0 (Antiviral Agents)
4FHH5G48T7 (Harmine)
0 (Carbolines)

Cyprinid herpesvirus 3

Date Created: 20250528 Date Completed: 20250528 Latest Revision: 20250531

20250531

PMC12115374

10.3390/v17050687

40431698