The severe acute respiratory syndrome (SARS)-like coronavirus disease (COVID-19) is caused by SARS-CoV-2 and has been a serious threat to global public health with limited treatment. Cellular heparan sulfate (HS) has been found to bind SARS-CoV-2 spike protein (SV2-S) and co-operate with cell surface receptor angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 infection of host cells. In this study, we determined that host cell surface SV2-S binding depends on and correlates with host cell surface HS expression. This binding is required for SARS-Cov-2 virus to infect host cells and can be blocked by heparin lyase, HS antagonist surfen, heparin, and heparin derivatives. The binding of heparin/HS to SV2-S is mainly determined by its overall sulfation with potential, minor contribution of specific SV2-S binding motifs. The higher binding affinity of SV2-S G614 mutant to heparin and upregulated HS expression may be one of the mechanisms underlying the higher infectivity of the SARS-CoV-2 G614 variant and the high vulnerability of lung cancer patients to SARS-CoV-2 infection, respectively. The higher host cell infection by SARS-CoV-2 G614 variant pseudovirus and the increased infection caused by upregulated HS expression both can be effectively blocked by heparin lyase and heparin, and possibly surfen and heparin derivatives too. Our findings support blocking HS-SV2-S interaction may provide one addition to achieve effective prevention and/treatment of COVID-19.
【저자키워드】 SARS-CoV-2, lung cancer, Spike protein, heparan sulfate, G614 mutant, 【초록키워드】 COVID-19, Treatment, coronavirus disease, ACE2, SARS-COV-2 infection, Infection, virus, angiotensin-converting enzyme 2, binding affinity, pseudovirus, SARS-CoV-2 spike protein, mutant, expression, mechanism, binding, Interaction, motifs, host cells, host cell, Support, acute respiratory syndrome, global public health, G614 variant, derivative, surface receptor, higher infectivity, derivatives, infect, effective, Cell, host cell surface, blocked, caused, addition, required, upregulated, lung cancer patient, the SARS-CoV-2, 【제목키워드】 spike, sulfate, Increased,