A Guide to Using Safer Endemic Coronaviruses to Model the More Pathogenic Strains

In 2021, at the height of the COVID-19 pandemic, coronavirus research spiked with over 83,000 original research articles related to the word “coronavirus” added to the online resource pubmed. Just 2 years later in 2023, only 30,900 original research articles related to the word “coronavirus” were added. While, irrefutably, the funding of coronavirus research has drastically decreased, another possible argument for the decrease in interest in coronavirus research is that projects on SARS-CoV-2, the causative agent of COVID-19, halted due to the challenge of establishing a good cellular or animal model system. Most laboratories do not have the capabilities to ‘in house’ culture SARS-CoV-2 as it requires a Biosafety Level (BSL) 3 laboratory. Until recently, BSL 2 laboratory research on endemic coronaviruses was arduous due to the low cytopathic effect in isolated cell culture infection models and lack of means to quantify viral loads. The purpose of this review article is to compare the human coronaviruses and provide an assessment of the latest techniques that use the endemic coronaviruses—HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1—as lower biosafety risk models for the more pathogenic coronaviruses – SARS-CoV-2, SARS-CoV, and MERS-CoV.