Table 3.

Evaluation of the antiviral activity of ivermectin in vivo in multicellular organisms.

Target virus and invertebrate hosts	Infection conditions	Quantitative and qualitative effects	References
Zika virus (Cambodia, FSS13025)	Aedes aegypti fed infected blood MOI = 0.5. Viral replication assessed in midgut 7 days post‐infection. Ivermectin at 10 nM.	Ivermectin had significant mosquitocidal effect but no effect on infection and replication of Zika virus in Aedes aegypti 7 days after infection. Control: 104(103–105) PFU/midgut, Ivermectin: 104 (102–105) PFU/midgut (n = 15)	[23]
West Nile virus (Colorado strain)	Wild Culex tarsalis trapped at pilot field trials sites with ivermectin‐treated bird feed (200 mg/kg diet) or control in an endemic area.	Ivermectin had no effect on bird health but was significantly mosquitocidal. Ivermectin had no effect on the number of Culex tarsalis pools and the average infection rates (MLE). Control: 14 (4–24), Ivermectin: 5 (0–9) (n = 136–1316)	[24]
Dengue virus‐2	Aedes albopictus (3–5 days) post‐larvae were fed with Dengue virus contaminated human blood for 4 days and then ivermectin in blood for 6 days at (0–64 ng/mL).	At (16, 32 and 64) ng/mL, ivermectin significantly reduced viral replication in Aedes albopictus. Control: 85 (81–90)%, Ivermectin 64 µg/mL: 43 (40–45)%. Ivermectin significantly inhibited viral replication. At 64 ng/mL, viral copies/mL reduced by 100 (84–100)% (n = 61–65)	[21]
Bluetongue virus (BTV‐17) Epizootic haemorrhagic disease virus (EHDV‐2)	Female Culicoides sonorensis were fed blood from ivermectin‐treated animals, mixed with viruses 7log10 TCID50 EHDV‐2 and 200 µg/kg ivermectin in elk blood. 7log10 TCID50 BTV‐17 and 400 µg/kg ivermectin in sheep blood.	Ivermectin significantly reduced infection and dissemination of BTV‐17. Control: 60%, Ivermectin 400 µg/kg: 18%. Ivermectin had no effect on infection and dissemination of EHDV‐2. Control: 40%, Ivermectin 200 µg/kg: 38% (n 100).	[13]
Gill parvovirus of crayfish and parvo‐like virus of crayfish	Fresh water crayfish with pre‐existing gill parvovirus were given ivermectin (3, 6 and 7 µg/kg, i.m). Ivermectin (7 µg/kg, i.m) was also given before, same day and after experimental infection with parvo‐like virus.	Ivermectin decreased the number of hypertrophied nuclei (68%) in gills of crayfish with pre‐existing parvo‐like virus. Control: 1591 ± 392.33 Ivermectin 3 µg/kg: 1039.85 ± 383.96 Ivermectin 7 µg/kg: 671 ± 379.07 (n = 20). Ivermectin modestly extended longevity of crayfish after experimental infection with parvo‐like virus.	[22]
Target virus and vertebrates hosts
Porcine circovirus‐2 (SH1 strain)	Piglets (30 days old) were infected (5 × 104 TCID50 i.m). Ivermectin (0.2 mg/kg i.m) at days 2, 4 and 6 post‐infection. Monitored 21 days	Ivermectin decreased replication; viral copies/titres in serum, brain, heart, kidneys, liver, lungs spleen and lymph nodes. Day 21 serum viral copies. Control: 5.1 (4.9–5.5) log10, Ivermectin: 2.4 (2.0–2.9) log10 (n = 3)	[25]
Zika virus (Senegal strain)	Five‐week‐old Ifnar1−/− mice were infected with 103 PFU in the footpad. Ivermectin (4 mg/kg, i.p), 2 days pre‐infection and then days 1, 2 and 4 post‐infection.	Ivermectin did not prevent infection or inhibit mortalities. Control: 100% mortality, Ivermectin =100% mortality (n = 7–8)	[26]
Suid herpesvirus 1	Female BALB/c mice (6–8 weeks old) were infected (~106 TCID50/mL). Ivermectin (0.2 mg/kg) at infection or at 12 hr post‐infection; 10 days monitoring.	Ivermectin inhibited replication; decreased viral DNA copies/titres in the brain and kidneys. Reduced mortality at day 7. Control: 100%, Ivermectin (at 12 hr) = 50% Ivermectin (at 0 hr) = 40% (n = 10)	[11]

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