CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

Abstract

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

Vigilance on New-Onset Atherosclerosis Following SARS-CoV-2 Infection

“…A current study elegantly found that CD147 can potentially bind to SARS-CoV-2, providing an additional infection route ( 51 ). CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily and expressed at varying levels in many cell types in its different glycoforms ( 52 ).…”

“…Similar to SARS-CoV-2-induced pulmonary damage, CD147 levels are increased in patients with chronic obstructive pulmonary disease ( 53 ). Meplazumab, a humanized anti-CD147 antibody, has been shown to inhibit SARS-CoV-2 replication in vitro ( 51 ). Recently, an open label, concurrent controlled add-on clinical trial in China revealed that the percentage of improvement in patients with severe COVID-19 presentations seems to be higher in patients receiving weekly treatment with meplazumab than in patients receiving conventional treatment.…”

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

“…In addition to ACE2, SARS-CoV-2 may infect various DC subsets through interaction with CD147, another receptor which binds SARS-CoV-2. The expression of CD147 by a non-susceptible cell line is sufficient to render it susceptible to infection [ 35 ] and it is expressed by DC [ 36 ]. moDC infected with SARS-CoV-1 produced significant amounts of pro-inflammatory chemokines, including MCP-1, MIP-1-α and IP-10.…”

Mucociliary Respiratory Epithelium Integrity in Molecular Defense and Susceptibility to Pulmonary Viral Infections

“…Based on in vitro experiments, Claussen and co-workers proposed a model of the heparan sulfate-mediated augmentation of SARS-CoV-2 binding to the ACE2 receptor [ 230 ]. Yet another novel mode of host entry and invasion by spike protein exploiting the CD147 receptor was recently demonstrated [ 231 ].…”