Abstract

COVID-19 is the most consequential pandemic of the 21st century. Since the earliest stage of the 2019-2020 epidemic, animal models have been useful in understanding the etiopathogenesis of SARS-CoV-2 infection and rapid development of vaccines/drugs to prevent, treat or eradicate SARS-CoV-2 infection. Early SARS-CoV-1 research using immortalized in-vitro cell lines have aided in understanding different cells and receptors needed for SARS-CoV-2 infection and, due to their ability to be easily manipulated, continue to broaden our understanding of COVID-19 disease in in-vivo models. The scientific community determined animal models as the most useful models which could demonstrate viral infection, replication, transmission, and spectrum of illness as seen in human populations. Until now, there have not been well-described animal models of SARS-CoV-2 infection although transgenic mouse models (i.e. mice with humanized ACE2 receptors with humanized receptors) have been proposed. Additionally, there are only limited facilities (Biosafety level 3 laboratories) available to contribute research to aid in eventually exterminating SARS-CoV-2 infection around the world. This review summarizes the most successful animal models of SARS-CoV-2 infection including studies in Non-Human Primates (NHPs) which were found to be susceptible to infection and transmitted the virus similarly to humans (e.g., Rhesus macaques, Cynomolgus, and African Green Monkeys), and animal models that do not require Biosafety level 3 laboratories (e.g., Mouse Hepatitis Virus models of COVID-19, Ferret model, Syrian Hamster model). Balancing safety, mimicking human COVID-19 and robustness of the animal model, the Murine Hepatitis Virus-1 Murine model currently represents the most optimal model for SARS-CoV-2/COVID19 research. Exploring future animal models will aid researchers/scientists in discovering the mechanisms of SARS-CoV-2 infection and in identifying therapies to prevent or treat COVID-19.

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), referred to as human coronavirus 19 (HCoV-19), is the virus that causes coronavirus disease (COVID-19)

  • While the MHV-S strain seems to have tropism comparable to the MHV-1 strain, which most exhibits the clinical disease progression and histopathology seen in COVID-19 patients, it has been shown by Körner et al (2020) that MHV-S has low virulence and is detected at low percentages in infected tissue, limiting its usefulness as a COVID-19 model when compared to more virulent MHV strains

  • Expansion of SARS-CoV-2 infection studies to non-human primates (NHPs) were explored in an effort to optimize animal models used in COVID-19 research, considering limitations that had been seen in rodents

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Summary

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), referred to as human coronavirus 19 (HCoV-19), is the virus that causes coronavirus disease (COVID-19). SARS-CoV-2 is an airborne virus that infects its host by first binding respiratory epithelium in the upper airways. At this time, the host may complain of non-specific flu-like symptoms (i.e. fever, fatigue, rhinorrhea). Regardless of SARS CoV-2’s exact infectious route, human cells have shown to be highly tropic to the virus, epithelial cells with human ACE-2 receptors, which line organs such as respiratory and GI tracts. Understanding how the virus infects its hosts is crucial in the production of vaccines that can help prevent disease (Chaudhari et al, 2021)

Variants of SARS-CoV-2
ANIMAL MODELS OF COVID 19
K18-hACE2 Transgenic Mouse Model
Mouse ACE2 Promoter With Human ACE2 Coding Sequence
Endogenous Mouse ACE2 Promoter Model
Adenovirus hACE2 Mouse Model for SARS-CoV-2 Infection
Mouse Hepatitis Virus Model
MHV-1 Virus De
Syrian Hamster Model
Ferret Models
Non-Human Primate Models
Rhesus Macaques Rhesus Macaques were used in the study of
Cynomolgus Macaques The
African Green Monkeys The African Green Monkey (AGM) model, demonstrated by
Cat Model
IN VITRO MODELS OF SARS-COV-2 INFECTION
Findings
CONCLUSION
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