Host Factors Enhancing SARS-CoV-2 Entry Discovered by HKUST Researchers Offers New COVID-19 Insights

Ground-breaking research at the Hong Kong University of Science and Technology (HKUST) has revealed new host features that help SARS-CoV-2 entry. This provides fresh knowledge of COVID-19's mechanism and possible therapy targets.

Discovery of New Host Factors

Under Prof. Guo Yusong, Associate Professor of the Division of Life Science at HKUST, the research team has identified more host components interacting with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Thus, the virus finds it simpler to enter host cells. Published in The Journal of Biological Chemistry, this study was performed with assistance from researchers from the University of Hong Kong (HKU) and the Hong Kong Polytechnic University (PolyU).

Scientists believe that SARS-CoV-2 enters host cells most of the time when the RBD of its spike protein interacts with the ACE2 receptor on these cells. Most research, however, simply examines what results from ACE2 overexpression. Not many studies look at what happens when ACE2 is removed. To fix this, the HKUST team used the GST pull-down method to find other host factors on the surface that bind to CoV2-RBD.

One important discovery was the identification of SH3BP4. This factor controls the uptake of CoV2-RBD and facilitates SARS-CoV-2 entry in a way that is not dependent on ACE2 but does depend on integrins and clathrins. This shows that SH3BP4 helps viruses enter cells through the endocytic pathway.

Also, ADAM9 and TMEM2 were more attracted to CoV2-RBD than to the less contagious SARS-CoV, which shows that they play a specific role in SARS-CoV-2 entry. Notably, some substances link more strongly to the RBD of the SARS-CoV-2 Delta variant, which might make it easier to enter cells.

Prof. Guo said these results show new host cell surface factors involved in SARS-CoV-2 invading cells. He emphasized how essential integrins are for helping viruses enter cells, which sets the stage for more studies that will lead to the development of COVID-19 treatments.

Mechanistic Insights and Therapeutic Potential

After finding these host factors, researchers better understand how SARS-CoV-2 gets into cells. Previous studies have mostly examined how the viral spike protein interacts with ACE2. This study shows that the virus can enter host cells in multiple ways.

In a related study, the urgent problem of highly contagious coronaviruses spreading from animals to people is still a significant issue. More recent research has shed much light on how SARS-CoV-2 gets into cells and determines its pathogenicity, host and tissue specificity, and zoonotic spread.

Some parts of the viral spike protein help the viral coat and host cell membrane join by attaching to ACE2. Also, host proteases like transmembrane protease serine two and cathepsins break down the spike protein, making it easier for the virus to enter. This affects both the endosomal and plasma membrane entry pathways.

Other host cofactors that assist SARS-CoV-2 in entering include neuropilin-1, CD147, phosphatidylserine receptors, heparan sulfate proteoglycans, sialic acids, and C-type lectins. Interferon-induced transmembrane proteins and lymphocyte antigen six complex locus E can prevent SARS-CoV-2 from entering, making them therapy targets.

The HKUST team's findings shed light on COVID-19's complexities and SARS-CoV-2's entry into the body. Researchers can identify more host characteristics that allow viruses to enter and develop novel treatments that target these pathways. This may improve COVID-19 and spider virus treatments.

The study's results on how viruses enter and interact with hosts molecularly demonstrate the importance of further research. Scientists learn about SARS-CoV-2's complex entry process, which opens the door to novel pandemic mitigation methods.