Abstract: Science of the Total Environment 808 (2022) 152072 Contents lists available at ScienceDirect Science of the Total Environment journal homepage: www.elsevier.com/locate/scitotenv Review CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target ⁎ ⁎⁎ Tapan Behl a, , Ishnoor Kaur a, Lotfi Aleya b, , Aayush Sehgal a, Sukhbir Singh a, Neelam Sharma a, ⁎ Saurabh Bhatia c, Ahmed Al-Harrasi c, Simona Bungau d, a Chitkara College of Pharmacy, Chitkara University, Punjab, India Chrono-Environment Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, France Natural & Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman d Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Romania b c H I G H L I G H T S G R A P H I C A L A B S T R A C T • Elaborating the severity of the COVID-19 pandemic and ACE-2-mediated entry of SARS-CoV-2 • Examining the relationship between malaria-causing Plasmodium falciparum receptor, CD147, and SARS-CoV-2 • CD147, evidently serving as an alternative entry receptor for viral entry • The catch and clump hypothesis • CD147 as a possible therapeutic target for effective candidates A R T I C L E I N F O Article history: Received 10 August 2021 Received in revised form 26 November 2021 Accepted 26 November 2021 Available online 1 December 2021 Editor: Damia Barcelo Keywords: COVID-19 ACE2 CD147 Receptor Catch and clump Melatonin A B S T R A C T 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. ⁎ Corresponding authors at: Chitkara College of Pharmacy, Chitkara University, Punjab, India. ⁎⁎ Co-corresponding author. E-mail addresses: tapanbehl31@gmail.com (T. Behl), simonabungau@gmail.com (S. Bungau). http://dx.doi.org/10.1016/j.scitotenv.2021.152072 0048-9697/© 2021 Elsevier B.V. All rights reserved. T. Behl et al. Science of the Total..