Table 2.

In vitro evaluation of the antiviral activity of ivermectin in cell cultures.

Target virus	Cell culture system and conditions	Quantitative and qualitative effects	References
West Nile virus (Kunjin; MRM61C strain), Zika virus (Asian/Cook Islands/2014 strain), Dengue virus‐2 (New Guinea C; M29095 strain).	Vero cells, MOI of 1 for 2 hr, followed for 22 hr. Ivermectin at (0–10 µM).	Concentration‐dependent inhibition of plague formation. EC50 West Nile virus = 0.8 µM EC50 Zika virus = 1.1 µM EC50 Dengue virus 0.4 µM Concentration‐dependent inhibition of replication. EC50 West Nile virus = 0.8 µM EC50 Zika virus = 1.9 µM EC50 Dengue virus 0.6 µM. (n = 2)	[8]
Dengue virus‐1 (EU081230), Dengue virus‐2 (EU081177), Dengue virus‐2 (mouse adapted S221)	Huh‐7 cells, MOI of 0.3 for 1 hr, followed for 48 hr. Ivermectin at (0–10 µM).	Concentration‐dependent inhibition of replication and plague formation. EC50 Dengue virus‐1 (EU081230) = 3.7 µM EC50 Dengue virus‐2 (EU081177) = 2.6 µM EC50 Dengue virus‐2 (S221) = 2.9 µM. (n = 2)	[7]
Dengue virus‐1 (EU081230), Dengue virus‐2 (EU081177), Dengue virus‐3 (EU081190), Dengue virus‐4 (GQ398256)	BHK‐21 cells, MOI of 0.3, followed for 48 hr and, Huh‐7 cells, MOI of 0.3 followed for 48 hr. Ivermectin at (0–45 µM).	Concentration‐dependent inhibition of replication. Values in BHK‐21 cells were: EC50 Dengue virus‐1 (EU081230) = 2.32 µM EC50 Dengue virus‐2 (EU081177) = 2.08 µM EC50 Dengue virus‐3 (EU081190) = 1.66 µM EC50 Dengue virus‐4 (GQ398256) = 1.90 µM Values in Huh‐7 cells were: EC50 Dengue virus‐1 (EU081230) = 2.97 µM EC50 Dengue virus‐2 (EU081177) = 1.74 µM (n = 2)	[6]
Wild type Chikungunya virus (LR2006 OPY1), Yellow fever virus (17D strain), Wild type Semliki Forest virus, Wild type Sindbis virus	BHK‐21 cells, MOI of 0.01, followed for 16 hr and, Huh‐7.5 cells, MOI of 0.1 followed for 16 hr. Ivermectin at (0–300 µM).	Time‐ and concentration‐dependent inhibition of replication. EC50 was evaluated for Chikungunya virus were: EC50 in BHK‐21 cells = 0.6 µM (n = 3) EC50 in Huh 7.5 cells = 1.9 µM. (n = 3) Ivermectin (3 µM) reduced viral titres in BHK‐21 cells by: 2.5 log values for Sindbis virus 3.0 log values for Semliki Forest virus 3.0 log values for Chikungunya virus 4.0 log values for Yellow fever virus	[51]
Yellow fever virus (17D strain), Dengue virus‐2 (New Guinea C strain)	Vero‐B cells, MOI of 0.4 for Dengue virus and 1.0 for Yellow fever virus. Followed for 168 hr. Ivermectin at (0–105 µM)	Ivermectin inhibited virus‐induced cytopathic effect. EC50 Yellow Fever virus (17D) = 0.005 µM EC50 Dengue virus‐2 (New Guinea) >1.0 µM	[52]
Yellow fever virus (17D strain), Dengue virus‐2 (New Guinea C strain), West Nile virus (NY99; NC‐009942)	Vero‐B cells for Dengue and Yellow Fever virus, MOI of 0.1 for 2 hr, followed for 96 hr. Vero‐E6 cells for West Nile virus, MOI of 0.1–1 for 2 hr, followed for 72 hr. Ivermectin at (0–5 µM).	Time‐ and concentration‐dependent inhibition of viral plication. EC50 Yellow Fever virus (17D) = 0.0005 µM EC50 Dengue virus‐2 (New Guinea) = 0.7 µM EC50 West Nile virus (NC‐009942) = 4.0 µM Ivermectin (0.01 µM) caused complete protection against Yellow Fever virus in the plague formation assay.	[4]
Dengue virus‐2 (New Guinea C strain), Pseudotyped NL4‐3.Luc.R‐E‐ HIV	Vero cells, MOI of 4 for Dengue virus, for 2 hr, followed for 72 hr and, Hela cells, 200 ng (capsid protein‐equivalent), for 2 hr, followed for 72 hr. Ivermectin (25 & 50 µM).	Concentration‐dependent inhibition of replication. Ivermectin at 25 and 50 µM inhibited Dengue virus production by 73% and 100% respectively. Ivermectin at 25 and 50 µM inhibited HIV virus production by 36% and 57% respectively. (n = 4)	[5]
Zika virus (PRVABC59 strain)	Vero cells, MOI of 0.1 for 1 hr, followed for 96 hr. Ivermectin at 10 µM.	Ivermectin (10 µM) reduced viral titres by 1.5 log values.	[53]
Zika virus (Cambodia, FSS13025)	C6/36 Aedes albopictus clone, MOI of 0.5, for 1 hr, followed for 5 days. Ivermectin tested at 2 and 10 µM.	Concentration‐dependent inhibition of replication. Ivermectin at 2 and 10 µM inhibited virus production by 34% and 62% respectively. EC50 >2 µM. (n = 3)	[23]
Porcine circovirus‐2 (SH1 strain)	PK‐15 cells, MOI of 10 for 1 hr, followed for 48 hr. Ivermectin at (57 and 114 µM).	Time‐ and concentration‐dependent inhibition of replication. Decreased by 59% at 24 hr and 72% at 48 hr for 57 µM of ivermectin, and by 81% at 24 hr and 84% at 48 hr for 114 µM of ivermectin. (n = 3)	[25]
Hendra virus (Australia/Horse/1994)	Vero cells, MOI of 0.05 for 2 hr, followed for 24 hr. Ivermectin at (0–10 µM).	Concentration‐dependent inhibition of replication. Viral titre decreased by 5 log values at 10 µM of ivermectin; EC50 = 2.0 µM. (n = 3)	[54]
Betaarterivirus (Porcine Reproductive and Respiratory Syndrome virus) (VR‐2332)	PAM‐pCD163 macrophages, MOI of 1 for 1 hr, followed for 48 hr. Ivermectin at (0–15 µM).	Time‐ and concentration‐dependent inhibition of viral replication. EC50 = 6.7 µM. At 15 µM of ivermectin, both infection and replication were reduced by 95%. No effect on adsorption and cell entry (n = 3)	[19]
Wild type BK Polyomavirus (BKPyV)	RPTE cells, MOI of 104 genomes/cell for 1 hr, followed for 24 hr. Ivermectin tested at 10 µM.	Ivermectin at 10 µM inhibited viral replication by 50%. (n = 3)	[55]
Venezuelan Equine Encephalitis virus (VEEV TC83)	U87MG cells, MOI of 0.1–1, followed for 24 hr. Vero cells, MOI of 0.1–1, followed for 24 hr. Ivermectin tested at 1 µM.	Ivermectin at 1 µM inhibited viral replication by 30% at 16 and 24 hr post‐infection in U87MG cells. No inhibitory effect was observed in Vero cells. Viral titres in plague assays were not affected at 24 hr post‐infection in both Vero and U87MG cells.	[9]
Venezuelan Equine Encephalitis virus (VEEV TC83)	Vero cells, MOI of 0.1, followed for 16 hr. Ivermectin tested at 1 µM.	No significant effect on viral titres in plague assays at 16 hr post‐infection in Vero cells. (n = 3).	[56]
Bovine herpesvirus‐1 (IBRV HB06 strain)	MDBK cells, MOI of 0.1–1 for 1 hr, followed for 48 hr. Ivermectin tested at (0–25 µM).	Dose‐dependent inhibition of viral replication. Viral titre decreased by 4 log values and, ~50% inhibition of virion production with 25 µM of ivermectin. No effect on viral attachment and cell entry. (n = 3).	[20]
Equine herpesvirus‐1 (Jan‐E strain) and (Rac‐H strain)	Primary murine neuronal cells, MOI of 0.3 for 1 hr, followed for 24 hr. Ivermectin tested at (0–75 µM).	No effect on the replication of EHV‐1 (Rac‐H strain). EC50 for EHV‐1 (Jan‐E strain) was >100 µM.	[57]
Suid herpesvirus 1	BHK‐21 cells, MOI of 0.01 for 1 hr, followed for 16–72 hr. Ivermectin at (0–2.5 µM).	Time‐ and concentration‐dependent inhibition of plague formation. Viral titres reduced by 23%, 68% and 70% for ivermectin concentrations of 0.5, 1.0 and 1.5 µM at 72 hr. No effect on adsorption and cell entry (n = 3)	[11]
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2 (Aus/VIC01/2020)	Vero/hSLAM cells, MOI of 0.1 for 2 hr, followed for 72 hr. Ivermectin tested at (0–10 µM).	Time‐ and concentration‐dependent inhibition of viral replication. Cell associated virus E‐gene EC50 = 2.8 µM Cell associated virus RdRp‐gene EC50 = 2.5 µM (n = 3).	[28]
Newcastle disease virus (LaSota vaccine strain)	9‐day chick embryos, 50% egg infective dose, followed for 6 hours. Ivermectin tested at (0–229 µM)	Dose‐dependent reduction of viral replication. Log2 reduction EC50 = (71 ± 33) µM (n = 5).	[58]

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