CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

Abstract

The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.

Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

“…2, CoV-Alt; however, further research is required to test their participation in the pathogenesis of COVID-19. For example, in vitro studies suggest that BSG (Basigin, also called CD147 or EMMPRIN, transmembrane glycoprotein belonging to the immunoglobulin superfamily) provides an alternate entry for SARS-CoV-2 when ACE2 and TMPRSS2 are not expressed [73][74][75]. We found that the placenta and chorioamniotic membranes expressed high levels of BSG throughout pregnancy (Fig.…”

Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis

“…[41,42,48,49]. CD147 is of particular interest because of the ongoing clinical trial that aims to treat SARS-CoV-2 with Meplazumab (a humanized anti-CD147 antibody) [39]. Importantly, for this subset of proteins, we conducted antibody staining to explicitly evaluate cell surface localization ( Fig.…”

“…including proteins suggested to be targets of S protein binding, including CD147 [39,40], Siglec 9 and 10 [41], as well as the host cell receptors for other coronaviruses, including CEACAM1, which is the receptor for Murine Coronavirus [42], and CD26 and CEACAM5, which are both receptors for MERS [43]. Expression and cell surface presentation of these putative receptors was validated using monoclonal antibodies ( Fig.…”

Is COVID-19 a New Hematologic Disease?

“…ACE2 stimulates mobilization of progenitor cells from bone marrow, migration to areas of vascular damage and revascularization of ischemic areas in pathological conditions like hypoxic exercise [6][7][8]. SARS-CoV-2 also probably invades host cells via CD147 (also known as Basigin or EMMPRIN) [9]. This CD147 has been also identified as a red blood cell receptor for parasite Plasmodium Falciparum [10] and a vascular receptor for Neisseria meningitidis [11].…”