SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

Wei, C.; Wan, L.; Yan, Q.; Wang, X.; Zhang, J.; Zhang, Y.; Sun, J.; Yang, X.; Gong, J.; Fan, C.; Wang, Y.; Li, J.; Yang, H.; Li, H.; Zhang, Z.; Wang, R.; Du, P.; Zong, Y.; Yin, F.; Zhang, W.; Peng, Y.; Lin, H.; Zhang, R.; Chen, W.; Gao, Q.; Cao, Y.; Zhong, H.

doi:10.1101/2020.08.13.248872

bioRxiv · 10.1101/2020.08.13.248872

SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

Wei, C.·Wan, L.·Yan, Q.·Wang, X.·Zhang, J.·Zhang, Y.·Sun, J.·Yang, X.·Gong, J.·Fan, C.·Wang, Y.·Li, J.·Yang, H.·Li, H.·Zhang, Z.·Wang, R.·Du, P.·Zong, Y.·Yin, F.·Zhang, W.·Peng, Y.·Lin, H.·Zhang, R.·Chen, W.·Gao, Q.·Cao, Y.·Zhong, H.

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Abstract

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

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Wei, C., Wan, L., Yan, Q., Wang, X., Zhang, J., Zhang, Y., Sun, J., Yang, X., Gong, J., Fan, C., Wang, Y., Li, J., Yang, H., Li, H., Zhang, Z., Wang, R., Du, P., Zong, Y., Yin, F., Zhang, W., Peng, Y., Lin, H., Zhang, R., Chen, W., Gao, Q., Cao, Y., Zhong, H.. 2020-08-14. SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry. https://doi.org/10.1101/2020.08.13.248872

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