SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Abstract

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion.Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC 50 of 24.86 μg/mL and IC 50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10 -7 M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

“…These data suggest mechanisms through which other CoVs could infect primary OSNs. We also note that CD147 has recently been identified as a cell surface SARS-CoV and CoV-2 interacting-molecule that may be involved in cell entry 72,73 . CD147 is expressed at high levels in both WOM and OSNs in non-human primates and humans (data not shown), although it remains unclear whether CoV-2-CD147 interactions are sufficient in the absence of ACE2 to mediate infection.…”

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

“…All these results provide insights that CD147 acts as a functional entry receptor for SARS-CoV-2, and serves as a therapeutic target for inhibiting virus infection. 13 It was reported 18.5% cases in COVID-19 were categorized as severe and critical cases, and fatality rate for critical case was 49.0% to 61.5%. 4,8 These studies reveal the great challenge of enhancing the therapeutic effects for severe case of COVID-19, and focus on how to conduct effective intervention as early as possible.…”

“…These data demonstrated a novel entry of virus infection mediated by CD147 receptor. 13 CD147 is also presented in activated inflammatory cells and participates the regulation of cytokine secretion and leukocytes chemotaxis by binding with cyclophilin A (CyPA). 14,15 CyPA is a proinflammatory cytokine that is up-regulated in response to virus infection.…”

Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells

“…S5a). Also, DMBT1 expression in AT2 cells was higher compared to other coronavirus receptors such as the MERS-CoV receptor DPP4 39,40 and BSG (also known as CD147) which was recently suggested to represent a potential alternate route of entry for SARS-CoV-2 41 (Fig. S5a).…”