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Review
. 2022 Feb 20:808:152072.
doi: 10.1016/j.scitotenv.2021.152072. Epub 2021 Dec 1.

CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target

Tapan Behl  1 , Ishnoor Kaur  2 , Lotfi Aleya  3 , Aayush Sehgal  2 , Sukhbir Singh  2 , Neelam Sharma  2 , Saurabh Bhatia  4 , Ahmed Al-Harrasi  4 , Simona Bungau  5
Affiliations
Review

CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target

Tapan Behl et al. Sci Total Environ. .

Abstract

The combat against the Corona virus disease of 2019 (COVID-19), has created a chaos among the healthcare institutions and researchers, in turn accelerating the dire need to curtail the infection spread. The already established entry mechanism, via ACE2 has not yet successfully aided in the development of a suitable and reliable therapy. Taking in account the constant progression and deterioration of the cases worldwide, a different perspective and mechanistic approach is required, which has thrown light onto the cluster of differentiation 147 (CD147) transmembrane protein, as a novel route for SARS-CoV-2 entry. Despite lesser affinity towards COVID-19 virus, as compared to ACE2, this receptor provides a suitable justification behind elevated blood glucose levels in infected patients, retarded COVID-19 risk in women, enhanced susceptibility in geriatrics, greater infection susceptibility of T cells, infection prevalence in non-susceptible human cardiac pericytes and so on. The manuscript invokes the title role and distribution of CD147 in COVID-19 as an entry receptor and mediator of endocytosis-promoted entry of the virus, along with the "catch and clump" hypothesis, thereby presenting its Fundamental significance as a therapeutic target for potential candidates, such as Azithromycin, melatonin, statins, beta adrenergic blockers, ivermectin, Meplazumab etc. Thus, the authors provide a comprehensive review of a different perspective in COVID-19 infection, aiming to aid the researchers and virologists in considering all aspects of viral entry, in order to develop a sustainable and potential cure for the 2019 COVID-19 disease.

Keywords: ACE2; CD147; COVID-19; Catch and clump; Melatonin; Receptor.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Unlabelled Image
Graphical abstract
Fig. 1
Fig. 1
Entry receptors of SARS-CoV-2: ACE2 and CD147. The ACE-2 receptor on the cell surface binds to the S-protein of the viral genome, thereby inducing conformational changes in the protein, which induces fusion of the viral envelope to the host cell membrane, followed by release of RNA into the host cell which undergoes translation and produces viral replicase polyproteins, cleaved to form proteinases. Irregular transcription and translation events lead to the formation of subgenomic mRNAs via RNA-dependent RNA polymerase (RDRP) enzyme, followed by viral proteins production. Like ACE-2, CD147 has also been identified as the binding site for the viral spike protein, elevated by angiotensin 2 and cyclophilins. Cyclophilin A and B bind to and activate CD147, thereby aiding in the process of interaction between viral S protein and CD147. SARS-CoV-2 enters the host cell through CD147 mediated endocytosis.
Fig. 2
Fig. 2
CD147 functioning as a receptor for malaria-causing Plasmodium falciparum and COVID-19, presenting the possible role of Azithromycin in COVID-19, on account of its potential in ameliorating malaria, by interfering with CD147 receptor. Anti-CD147 antibody therapy hinders invasion of SARS-CoV-2 and plasmodium falciparum, however, the impact of azithromycin on SARS-CoV-2 is yet to be investigated further. The concentration of interferons and interferon-stimulated proteins is elevated and viral replication and release id retarded, via which the anti-viral responses are induced in the endothelial cells.
Fig. 3
Fig. 3
Role of melatonin in minimizing the SARS-CoV-2 – mediated infection in host cell. Melatonin has been reported to inhibit CD147-mediated signalling pathway and retards serum cytokine (TNF-α, MCP-1, IL-6 and INF-γ) levels, mediated by CD147, which exhibit a significant involvement in inflammation, thereby retarding tissue injury and cytokine storm. [CD147 – cluster of differentiation 147; SARS-CoV-2 – severe acute respiratory syndrome coronavirus 2; TNF-α – tumour necrosis factor; MCP-1 – monocyte chemoattractant protein 1; IL-6 – interleukin-6; INF-γ – interferon-gamma].
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