A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories.

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 . 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 drastically decreased, a possible explanation 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 culture SARS-CoV-2 'in house' as this 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 the 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, and HCoV-HKU1-as lower-biosafety-risk models for the more pathogenic coronaviruses-SARS-CoV-2, SARS-CoV, and MERS-CoV.