SARS-CoV-2 Entry: At the Crossroads of CD147 and ACE2

Abstract

In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi’s sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. In particular, SARS-CoV recognizes the CD147 receptor expressed on the surface of host cells by its nucleocapsid protein binding to cyclophilin A (CyPA), a ligand for CD147. However, the involvement of CD147 in SARS-CoV-2 infection is still debated. Interference with both the function (blocking antibody) and the expression (knock down) of CD147 showed that this receptor partakes in SARS-CoV-2 infection and provided additional clues on the underlying mechanism: CD147 binding to CyPA does not play a role; CD147 regulates ACE2 levels and both receptors are affected by virus infection. Altogether, these findings suggest that CD147 is involved in SARS-CoV-2 tropism and represents a possible therapeutic target to challenge COVID-19.

Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors

“…Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported, great efforts have been made to understand how the virus enters target cells [ 1 ]. The spike protein, a surface protein present in other coronaviruses such as SARS-CoV-1 and MERS-CoV, has been shown to be primarily responsible for the ability of SARS-CoV-2 to interact with receptors expressed on the membrane of host cells [ 1 ].…”

“…Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported, great efforts have been made to understand how the virus enters target cells [ 1 ]. The spike protein, a surface protein present in other coronaviruses such as SARS-CoV-1 and MERS-CoV, has been shown to be primarily responsible for the ability of SARS-CoV-2 to interact with receptors expressed on the membrane of host cells [ 1 ]. Several proteins have been described that act as facilitators of the interaction between the virus and the target cells, such as neuropilin 1 (NRP1) [ 1 , 2 ], FURIN protease [ 3 ], transmembrane serine 2 (TMPRSS2) [ 3 ] and angiotensin converting enzyme 2 (ACE2) [ 4 ].…”

Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants

“…Indeed, it plays an essential role in promoting viral infection exerting its functions both inside and outside host cells. In particular, CyPA (i) acts as an intracellular chaperone during viral replication for different viruses ( 33 , 34 ); (ii) behaves as an intracellular sensor that favors viral infection (hampering the innate immune response [ 35 ], and regulating the sensitivity to host restriction factors [ 36 ]); and (iii) partakes in target cells invasion by HIV-1 and SARS-CoV ( 51 – 53 ), but not by SARS-CoV-2 ( 54 ), mediating virus binding to the CD147 receptor. Furthermore, CyPA has been recently reported as the top ranked hit in a meta-analysis study of host genes implicated in COVID-19 ( 37 ).…”

Structural biology of SARS-CoV-2: open the door for novel therapies

“… 65 , 66 Inhibitors of furin protease include decanoyl-RVKR-chloromethylketone (CMK) 67 and a-1 antitrypsin Portland (a1-PDX). 68 There are other known host receptors of S protein, such as glucose-regulated protein 78 (GRP78) 69 and CD147, 70 which could also be targeted.…”