Seasonal Coronavirus Enters Human Cells via Identified Receptor Revealing Virulence Differences

Research published in Nature has identified the receptor used by the seasonal coronavirus HKU1 to enter human cells, which differs from SARS-CoV-2, providing insights into why one coronavirus is more severe than another and potentially aiding in the development of targeted therapies. 

The SARS-CoV-2 virus responsible for COVID-19 causes severe acute respiratory syndrome, unlike other coronaviruses that usually cause mild colds. This divergence in severity between different coronaviruses prompted researchers at the Institut Pasteur, Université Paris Cité, and the VRI to investigate further.  

HKU1 is one of 7 coronaviruses known to infect humans and mainly targets upper respiratory tract cells. It is similar to SARS-CoV-2 in terms of infectivity and can lead to severe infections in vulnerable individuals such as young children and the elderly and has a high rate of exposure in the global population. The cleaving of coronavirus spike proteins, essential for viral fusion, entry, and multiplication, occurs at the cellular level after binding to their receptors, with ACE2 serving as the gateway for entry in certain coronaviruses (SARS-CoV-2 and NL63), while the receptors for HKU1 and OC43 remained unknown previously.  

The study revealed that the seasonal coronavirus HKU1 uses the TMPRSS2 enzyme gateway to enter human cells, unlike SARS-CoV-2. This difference in receptor binding could contribute to the contrasting levels of severity observed between these two coronaviruses.  

"Once a receptor has been identified for a virus, it is possible to characterize target cells more accurately, while also gaining insights on viral entry and multiplication mechanisms and infection pathophysiology," said researchers.  

Understanding the route of viral entry into cells could aid in the development of targeted therapies and evaluating the virulence risk of future coronaviruses. Additionally, the Institut Pasteur research teams have created and characterized nano-antibodies that can hinder HKU1 infection by attaching to the TMPRSS2 receptor, potentially providing therapeutic benefits through patented reagents. 

Reference 

Myriam R. New discovery concerning receptors used by coronaviruses to enter human cells. EurekAlert! Published online October 27, 2023. Accessed November 14, 2023. https://www.eurekalert.org/news-releases/1006157