Abstract
Animal models have been critical in understanding the pathogenesis, transmission, and therapeutic interventions for COVID-19, caused by SARS-CoV-2. The primary challenges include species-specific differences in viral receptor expression, particularly the ACE2 receptor, and immune system responses, which can affect how closely these models mimic human COVID-19 pathology. Additionally, ethical concerns around the use of animals, especially non-human primates, and logistical issues such as high costs, housing requirements, and limited availability of certain models, further complicate research efforts. Transgenic mice expressing human ACE2 (hACE2) are widely used because of their ease of handling and cost-effectiveness. Other animal models include non-human primates, hamsters, cats, and ferrets, which were used to study viral transmission and host-pathogen interactions. The rapid dynamics of the SARSCoV-2 evolution is one of the challenges and the complementary use of multiple models provides a more comprehensive understanding of the disease. Nonetheless, these models have been essential for rapid advancements in COVID19 vaccine and therapeutic development, offering insights that continue to guide public health strategies. The review discusses the various animal models used in SARS-CoV-2 research, the outcomes, and the challenges and questions to be addressed Keywords: Animal models, SARS-CoV-2, COVID-19
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