Novel host factors identified as important for SARS-CoV-2 infection

A research team led by Professor Guo Yusong, Associate Professor of the Division of Life Sciences at the Hong Kong University of Science and Technology (HKUST), recently made a new discovery related to the coronavirus (SARS-CoV-2) that causes COVID-19. The team identified novel host factors that interact with the receptor binding domain of the SARS-CoV-2 spike protein to promote viral entry. This discovery provides valuable mechanistic insights and potential therapeutic strategies against SARS-CoV-2 infection.

It is generally accepted that SARS-CoV-2 enters host cells through the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and the host cell receptor ACE2, thereby facilitating viral invasion. However, most evidence relies on the overexpression of ACE2 to promote viral entry, and few studies have been conducted to determine whether complete knockdown of ACE2 inhibits viral entry. To address this issue, the HKUST research team led by Professor Guo, in collaboration with research teams from The University of Hong Kong (HKU) and The Hong Kong Polytechnic University (PolyU), identified other novel surface-located host factors, in addition to ACE2, that also bind to CoV2-RBD using the GST pull-down method.

The experiment demonstrates that among the factors, one in particular called SH3BP4, regulates the internalization of CoV2-RBD and facilitates the entry of the SARS-CoV-2 pseudovirus in a manner that depends on integrins and clathrin, but not on ACE2, implying that SH3BP4 promotes viral entry via the endocytosis pathway. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, exhibit higher affinity for the RBD of CoV2 compared to the RBD of the less infectious SARS-CoV, indicating their specific use for SARS-CoV-2. Furthermore, this study reveals factors that preferentially bind to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry.

“These results identify novel host cell surface factors involved in SARS-CoV-2 invasion and highlight the crucial role of integrins in mediating viral internalization, thereby establishing new research foundations for the treatment of COVID-19.”

Professor Guo Yusong, Associate Professor, Division of Life Sciences, Hong Kong University of Science and Technology

The study was recently published in the international academic journal, Journal of Biological ChemistryThe research team also consists of Professor CHEN Honglin from the Department of Microbiology, HKU; and Professor YAO Zhongping, from the Department of Applied Biology and Chemical Technology, PolyU; and their team members.