The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy

Abstract

As a result of the conducted experimental studies on intranasal challenge of ICR mice, rabbits and miniature pigs (even in the maximum variant) with the doses of 4.0-5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50% infective dose (C ID50 ) of MPXV for these animals estimated by the presence of external clinical signs was 4.8 lg PFU, and L ID50 estimated by the virus presence in the lungs of mice 7 days post-infection taking into account its 10% application in the animal respiratory tract was 1.4 lg PFU. When studying the dynamics of MPXV propagation in mice challenged intranasally with 25 L ID50 of MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and brain: 5.7 ± 0.1, 5.5 ± 0.1 and 5.3 ± 0.3 lg PFU/ml, respectively. The pathomorphological examination of these animals revealed the presence and replication of the pathogen in the traditional primary target cells for MPXV (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well as in some other types of cells (endothelial cells, reticular cells, connective tissue cells). Our use of these animals to assess the antiviral efficacy of some drugs demonstrated the agreement of the results (a significant positive effect of NIOCH-14 and ST-246) with those described in scientific literature, which opens up the prospects of using ICR mice as animal models for monkeypox to develop preventive antismallpox drugs.

Using the Ground Squirrel (Marmota bobak) as an Animal Model to Assess Monkeypox Drug Efficacy

“…However, the conducted information analysis, concerning epidemic‐prone viral diseases (smallpox, influenza, adenovirus and rhinovirus infections, etc.) whose basic mechanisms of transmission resemble those of monkeypox (aerosol and contact ones) and are implemented primarily through the respiratory tract, suggests that the susceptibility of unvaccinated individuals to MPXV is quite high and does not exceed 100 PFU (Sergeev et al., ). The susceptibility of marmots (about 160 PFU) is close to that of humans.…”

Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives

“… Bioluminescence imaging in MPXV infected mice revealed that the virus was more replicated in the head and virus plaques quantitatively were seen in brain tissues Zaire strain (MPXV-z06) Earl et al [ 60 ] ICR mice i.n. Plaque assay indicated that increased the MPXV values in homogenized animal brain tissues Central African clade (V79-1–005) Sergeev et al [ 61 ] i.n. intranasal, i.p.…”

“…Additionally, subcutaneously injection of MPXV in cynomolgus monkeys strongly increased viral particles in the alveolar and mediastinal lymph node macrophages detected by electron microscopy, indicating a high replication process in these cells [ 63 , 64 ]. Also, the viral particles have been obviously detected after intranasal inoculation of MPXV in activated alveolar macrophages of ground squirrels, mice, and prairie dogs as shown by electron microscopy images [ 16 , 59 , 61 ]. It should be mentioned that the current data suggest the possible neuroinvasive potential of MPXV; however, more broadly, research is also needed to determine the exact invasion routes.…”

Smallpox, Monkeypox and Other Human Orthopoxvirus Infections

“…An ST-246 analogue called NIOCH-14 also showed high activity against orthopoxvirus infections in various animal models [ 132 , 133 , 134 , 135 ]. After the completion of preclinical and clinical trials, NIOCH-14 was approved for clinical use in Russia in October 2022.…”