Anti-monkeypox Drug Discovery In Vivo Assays in Animal Models

The utility of a small animal model of human disease for the study of therapeutic efficacy is augmented when large numbers of animals are available for use in appropriately, well-powered studies. Creative Biolabs is a global provider of in vivo and in vitro assays for anti-monkeypox drug discovery. All assessments are performed by qualified and experienced professionals.

The Significance of Animal Models for Anti-Monkeypox Drug Discovery

Animal models permit an advance beyond what can be gleaned from tissue culture evaluation of an antiviral effect. The evaluation of an antiviral, in the context of a host with a functioning immune system, enables a better understanding of therapeutics' potential efficacy. The evaluation of an antiviral in the context of an impaired immune system enables a better understanding of therapeutic use in a particular immunosuppressed population. Many newly developed or refined mouse, African dormouse, ground squirrel, rabbit, and monkey models are available for studying the treatment of orthopoxvirus infections. Investigations have led to the discovery of orally active inhibitors of orthopoxvirus infections in animals. In considering the use of any animal model, species differences in drug pharmacology and metabolism must be taken into account when evaluating the differences seen in the antiviral activity demonstrated.

Animal Models at Creative Biolabs

Novel small animal species have been used or are being studied as models for the treatment of monkeypox virus (MPXV) infections. These include dormice and American ground squirrels. Rabbits are being used more widely to study the treatment of orthopoxvirus infections. These and other models are important to establish the efficacy of new antiviral compounds to satisfy the animal efficacy rule for drug development against orthopoxvirus infections. To date, four MPXV small animal models have been used for the testing of antiviral drugs. Of the small animal models used to evaluate antiviral efficacy, all have used stringent virus challenges and shown survival benefits.

• African Dormouse

It is a mouse-sized rodent found in areas of Africa where human monkeypox has occurred. It is susceptible to a lethal infection of MPXV and MPXV replicated in multiple organs of this species. The dormouse model was validated for testing prophylactic and therapeutic test articles against intranasal challenges with MPXV.

• Ground Squirrels

Ground squirrels are very susceptible to MPXV infection. They might be an excellent small-animal model for studying the pathogenesis and treatment of severe orthopoxvirus infections in people.

• Rabbits

Rabbits have also been considered as a possible animal model for the study of MPXV, susceptibility depended greatly on the method of inoculation and the age of the animals.

• Prairie Dogs

Prairie dogs have also been looked at as a possible MPXV animal model.

Fig.1 Proposed model for MPXV pathogenesis within prairie dogs.¹

In Vivo Assays at Creative Biolabs

Animal models are used for in vivo study of potential virus inhibitors with a variety of parameters used to indicate the severity of the infection and its inhibition by therapy. Multiple parameters are recommended in any in vivo antiviral evaluation. One of the more qualitative discovery challenges is to improve the predictability of early-stage research models in terms of in vivo drug efficacy.

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