Table 2.
Exploratory antiviral studies of ivermectin in animal viruses: epidemiology, experimental context, experimental evidence category, and proposed mechanism.
| Virus | Worldwide incidence | Experimental context | Experimental evidence category | Proposed mechanism |
|---|---|---|---|---|
| Foot and Mouth Disease Virus (FMDV) | Worldwide: 1.8% of cattle, 1.5% of goats, 1.4% of pigs, 1.0% of sheep (31) |
In vitro + in vivo | Preclinical data (32). Lack of efficacy against serotype O in mice (33) |
Unknown |
| Hendra Virus (HeV) | Humans: 1.68 cases per year 0.13 deaths per year, localized to Australia (1994–2015) (53) Horses: 3 cases per year, 2.7 deaths per year (53) |
In vitro | Preclinical (54) | Inhibition of importin α (54) |
| Newcastle Disease Virus (NDV) | In an Indian study, Newcastle disease affected 14% of commercial birds (46) Not common in North America and Europe, controlled by vaccination (47) |
In vitro + animal trial | Preclinical: Antiviral effect at 100 μg/mL IVM, but also cytotoxicity (48) Animal Trial: Laying hens with NDV showed improvement when treated with IVM (50) |
Potentially importin α1/β1 (48) |
| Infectious Laryngotracheitis Virus (ILTV) | Prevalence of 13% of commercial poultry in Ethiopia (35) | Animal trial | Animal Trial: Laying hens with ILTV showed improvement when treated with IVM (34) | Unknown |
| Equine Herpesvirus (EHV) | EHV-1: >60% of horses worldwide (55) EHV-4: ~66% of horses (56) |
In vitro | Preclinical: Some reduction of replication in EHV-1 strain Jan-E replication but not strain Rac-H (57) | Importin α/β disruption (57) |
| Pseudorabies Virus (PRV) | 3% of domestic pigs in a Croatian study (34) | In vitro | Preclinical: Reduction of PRV proliferation in BHK-21 cells (35) and Vero cells (36) | Inhibition of DNA polymerase UL42 (35) |
| Porcine Circovirus 2 (PCV2) | 57% PCR test positivity in Chinese study (37) | In vitro + in vivo | Preclinical: Inhibition of PCV2 replication in PK-15 cells (38) Animal Trial: Mitigation of PCV2 infection in piglets (38) |
Disruption of nuclear import (38) |
| Bovine Respiratory Syncytial Virus (BRSV) | 10.8% (58) | In vitro | Preclinical: Inhibition of BRSV replication in vitro (MDBK cell line) (59) | Postulated: Importin α/β inhibition |
| Bovine Parainfluenza Virus Type 3 (BPIV-3) | 0.64% (60) 13.5% (58) |
In vitro | Preclinical: Inhibition of BPIV-3 replication in vitro (MDBK cell line) (59) | Postulated: Importin α/β inhibition |
| Bovine Herpesvirus 1 (BoHV-1) | 5.4% (62) | In vitro | Preclinical: Inhibition of BoHV-1 replication in vitro (MDBK cell line) (59) | Postulated: Importin α/β inhibition |
| Bovine Coronavirus (BCoV) | 32.4% (58) | In vitro | Preclinical: Inhibition of BCoV replication in vitro (MDBK cell line) (59) | Postulated: Importin α/β inhibition |
| Bovine Viral Diarrhea Virus (BVDV) | ≤0.8% in Europe, North America, and Australia to >1.6% in West Asia (61) | In vitro | Preclinical: Inhibition of BVDV replication in vitro (MDBK cell line) (59) | Postulated: Importin α/β inhibition |
| Varicellovirus Bovinealpha 1 (BoAHV-1) | 21.43% (63) | In vitro | Preclinical: Inhibition of BVDV replication in vitro (MDBK and BT cell lines) (64) | Unknown |
| Malignant Catarrhal Fever (alcelaphine herpesvirus 1) (AHV-1) | In Kenya, causes loss of up to 10% of cattle herds per year (65) | In vitro | Preclinical: Inhibition of viral replication in vitro (BT1621 cell line) (66) | Potentially inhibition of nuclear transport (66) |
| Infectious Bovine Rhinotracheitis Virus (IBRV) | 3.4% of cattle in a Mexican survey (67) | In vivo | Animal Trial: Inhibition of viral replication in a rabbit model (68) | Unknown, but IVM did not affect viral binding and entry (68) |
| Lumpy Skin Disease Virus (LSDV) | 54% of cattle in Africa (39) | In vitro | Preclinical: Strong inhibition in vitro at the viral replication stage (99.8%), attachment stage (68.4%), and penetration stage (57.8%) (40) | Unknown |
| Sheep Pox (SPPV) | 2% (Northern Nigeria) (41) 16% (Amhara, Ethiopia) (42) |
In vitro | Preclinical: Strong inhibition in vitro at the viral replication stage (99.9%), weak inhibition at the attachment stage (25.1%), and no inhibition at the penetration stage (0.0%) (40) | Unknown |
| Porcine Epidemic Diarrhea Virus (PEDV) | Resulted in a loss of almost 10% of US domestic pig production (43) | In vitro | Preclinical: Inhibition of PEDV replication in Vero cells (36, 44) and porcine LLC-PK1 cells (36) | Potential disruption of nuclear import (36) |
| Swine Vesicular Stomatitis Virus (VSV) | Low incidence (0.2%) in feral swine in the USA, possibly endemic to other regions (45) | In vitro | Preclinical: Inhibition of VSV in Vero cells (36) | Unknown |
| Peste des Petits Ruminants Virus (PPRV) | 79–100% of cattle (Sudan) (61) | In vitro | Preclinical: Inhibition of replication in Vero cells, but limited effect on viral entry (63) | Unknown |
| Viral Hemorrhagic Septicemia Virus (VHSV) | 72.4% of cattle (65) | In vitro + in vivo | Preclinical: Inhibition in EPC cells (66) Animal Trial: Better survival rates in VSHV-infected olive flounder (66) |
Unknown |
| Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) | 11 to 32% of pigs (66) | In vitro + in vivo | Preclinical: Inhibition of replication in PAM-pCD163 cells (67) Animal Trials: May have reduced lung lesions in veterinary trials (68) |
Inhibition of viral entry, no inhibition of nuclear import (67) |
| Usutu Virus (USUV) | 105 cases in humans, several outbreaks in birds and mosquitoes (69) | In vitro | Preclinical: Inhibition in Vero CCL-81, A549 and TME-R cells (70) | Inhibition of flaviviral non-structural protein 3 (71) |
| Parvoviruses (PV) | Porcine parvoviruses, 19.6% (72) | In vivo | Animal Trial: Lower levels of hypertrophied nuclei in parvovirus-infected crayfish administered IVM (73) | Putatively nuclear localization disruption (73) |
| Papillomaviruses (PV) | Papillomavirus affects 4.4% of cattle (74) | In vivo / observational | Animal Trial: No remission from bovine cutaneous papillomatosis in the control group, 83% remission in IVM groups (75) Cattle given IVM had regression of cutaneous papilloma (74) Improved healing of udder papillomaviruses in goats (75) Improvement in equine papillomatosis symptoms with oral IVM administration (76) Complete remission in heifer and calf papillomatosis (77) |
Unknown |
| Avian Infectious Bronchitis Virus (IBV) | ~40% (Spain) broiler chickens in (51) | In vitro | Preclinical (negative): Lack of efficacy in preclinical experiments (52) | N/A |
| Bluetongue Virus (BTV) | 1% of cattle in a Florida sample (63) | In vitro | Preclinical: No effect observed in vitro (64) | N/A |