Eda Baldan TOKER, Özer ATEŞ, Kadir YEŞİLBAĞ

İvermektinin Küçük Ruminant Vebası (PPR) Virusuna Karşı İn Vitro Antiviral Etkinliği

Küçük ruminant vebası (PPR), koyun ve keçi yetiştiriciliğinde önemli ekonomik kayıplara neden olan ve Dünya Hayvan Sağlığı Örgütü tarafından bildirimi zorunlu hastalıklar listesinde yer alan bir hastalıktır. Hastalığı kontrol altında tutmanın en etkili çözümü aşı uygulamaları olsa da, enfeksiyonun ortaya çıktığı durumlarda Küçük ruminant vebası virusuna (PPRV) doğrudan etki gösteren bir antiviral ilaç bulunmamaktadır. Nematodlara karşı uygulanan geniş spektrumlu bir antiparaziter ajan olan ivermektinin (IVM) son yıllarda çeşitli viruslara karşı in vitro antiviral aktiviteye sahip olduğu da bildirilmiştir. Bu çalışmada, PPRV’nin hücreye tutunma, giriş ve replikasyon aşamalarında IVM’in antiviral aktivitesinin değerlendirilmesi amaçlanmıştır. Vero hücrelerinde IVM’nin viral replikasyon aşamasındaki etkinliğini değerlendirmek için, IVM ile muamele edilmeyen ve non-sitotoksik IVM konsantrasyonları (1 ve 2,5 μM) ile tedavi edilen PPRV’nin viral titreleri enfeksiyon sonrası 8 gün boyunca karşılaştırıldı. 2,5 μM IVM varlığında PPRV’nin replikasyon aşamasında ortalama viral titre değerlerinde l,12 log10 DKID50/0,1ml düzeyinde düşüş ile önemli oranda azalma görüldü (P

Anahtar Kelimeler:

İvermektin, Antiviral etkinlik, İn vitro test, Peste des petits ruminants virus, PPR

In Vitro Antiviral Efficiency of İvermectin Against Peste des Petits Ruminants (PPR) Virus

Peste des petits ruminants (PPR) cause significant economic losses in sheep and goat breeding and are listed as notifiable diseases by the World Animal Health Organization. Although vaccination is the most effective solution for control of PPR, there is no antiviral drug that directly affects the PPR virus (PPRV). In recent years, Ivermectin (IVM), a broad-spectrum antiparasitic, has also shown in vitro antiviral activity against several viruses. In this study, we aimed to investigate the antiviral efficiency of IVM at the stages of viral replication, cell-attachment and cell-entry of PPRV. To evaluate the efficacy of IVM at the viral-replication stage in Vero cells, the viral titers from PPRV infected cultures treated with non-cytotoxic IVM concentrations (1 and 2,5μM) were compared to titers from PPRV infected cultures without IVM by virus titration assay for 8 days. In the presence of 2,5μM IVM, the mean viral titers at the virus replication stage were significantly reduced by 1,12log10 TCID50/0,1ml (P

Keywords:

Ivermectin, Antiviral efficiency, In vitro testing, Peste des petits ruminants virus, PPR,

PDF

___

OIE. Peste des Petits Ruminants. Cent Food Secur Public Heal. Published online 2015:1-5. https://www.cfsph.iastate.edu/
OIE, FAO. Global Strategy for the Control and Eradication of PPR.; 2015.
ICTV. Taxonomic Information-International Committee on Taxonomy of Viruses. https://talk.ictvonline.org/.
Muniraju M, Munir M, Parthiban AR, et al. Molecular evolution of peste des petits ruminants virus. Emerg Infect Dis. 2014;20(12):2023-2033. doi:10.3201/eid2012.140684
ViralZone. SIB Swiss Institute of Bioinformatics. https://viralzone.expasy.org/.
Baron MD, Parida S, Oura CAL. Peste des petits ruminants: A suitable candidate for eradication? Vet Rec. 2011;169(1):16-21. doi:10.1136/vr.d3947
Kgotlele T, Chota A, Chubwa CC, et al. Detection of peste des petits ruminants and concurrent secondary diseases in sheep and goats in Ngorongoro district, Tanzania. Comp Clin Path. 2019;28(3):755-759. doi:10.1007/s00580-018-2848-5
Zhao H, Njeumi F, Parida S, Benfield CTO. Progress towards eradication of peste des petits ruminants through vaccination. Viruses. 2021;13(1):1-15. doi:10.3390/v13010059
Campbell WC, Fisher MH, Stapley EO, Albers-Schonberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent. Science (80- ). 1983;221(4613):823-828. http://www.sciencemag.org/cgi/content/abstract/221/4613/823
Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-856. doi:10.1042/BJ20120150
Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res. 2020;177(December 2019):104760. doi:10.1016/j.antiviral.2020.104760
Azeem S, Ashraf M, Rasheed MA, Anjum AA, Hameed R. Evaluation of cytotoxicity and antiviral activity of ivermectin against Newcastle disease virus. Pak J Pharm Sci. 2015;28(2):597-602.
Mastrangelo E, Pezzullo M, De burghgraeve T, et al. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: New prospects for an old drug. J Antimicrob Chemother. 2012;67(8):1884-1894. doi:10.1093/jac/dks147
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res J. 2020;178(January):104787.
Afzal S, Raza S, Rabbani M, Firyal S, Altaf I, Naeem Z. Antiviral Potential of Ivermectin against Peste des Petits Ruminants Virus (PPRV). Pakistan J Zool. Published online 2021:1-4. doi:https://dx.doi.org/10.17582/journal.pjz/20200704060712
Naeem Z, Raza S, Afzal S, Sheikh AA, Ali MM, Altaf I. Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1. Microb Pathog. 2021;155(April):104914. doi:10.1016/j.micpath.2021.104914
Yesilbag K, Toker EB, Ates O. Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro. Virus Res. 2021;297(December 2020):198384. doi:10.1016/j.virusres.2021.198384
Lv C, Liu W, Wang B, et al. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antiviral Res. 2018;159(August):55-62. doi:10.1016/j.antiviral.2018.09.010
Raza S, Shahin F, Zhai W, et al. Ivermectin inhibits bovine herpesvirus 1 DNA polymerase nuclear import and interferes with viral replication. Microorganisms. 2020;8(3):1-15. doi:10.3390/microorganisms8030409
Varghese FS, Kaukinen P, Gläsker S, et al. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res. 2016;126:117-124. doi:10.1016/j.antiviral.2015.12.012