Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

Helal, Mohamed A.; Shouman, Shaimaa; Abdelwaly, Ahmad; Elmehrath, Ahmed O.; Essawy, Mohamed; Sayed, Shireen M.; Saleh, Amr Hany; El‐Badri, Nagwa

doi:10.1080/07391102.2020.1822208

Cited by 78 publications

(82 citation statements)

References 93 publications

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“…Despite the importance of determining precisely which entry receptors SARS-CoV-2 uses to infect human cells, there remains considerable uncertainty amid multiple claims of several viral receptors with variable qualities of data to support these assertions 8,[33][34][35][36] . We investigated one of the most prominent claims, that human BSG acts as an alternate receptor for the virus to interact with, which has been the topic of several studies, news and review articles, and a clinical trial 10,14,15,[37][38][39][40][41][42] . Our access to established tools and reagents from previous work studying BSG's role as a host receptor in Plasmodium infection allowed us to rapidly investigate BSG as a SARS-CoV-2 receptor.…”

Section: Discussionmentioning

confidence: 99%

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts

Crozier

Greenwood

et al. 2021

Sci Rep

163

137

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The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses speculating on the role of this host receptor in viral infection and pathogenesis. Here, we report that we are unable to find evidence supporting the role of basigin as a putative spike binding receptor. Recombinant forms of the SARS-CoV-2 spike do not interact with basigin expressed on the surface of human cells, and by using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for a direct interaction between the viral spike protein to either of the two common isoforms of basigin. Finally, removing basigin from the surface of human lung epithelial cells by CRISPR/Cas9 results in no change in their susceptibility to SARS-CoV-2 infection. Given the pressing need for clarity on which viral targets may lead to promising therapeutics, we present these findings to allow more informed decisions about the translational relevance of this putative mechanism in the race to understand and treat COVID-19.

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Section: Discussionmentioning

confidence: 99%

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts

Crozier

Greenwood

et al. 2021

Sci Rep

163

137

View full text Add to dashboard Cite

show abstract

“…The CD147 (also known as basigin) has also been reported as an entry route for SARS-CoV-2 into host cells ( 22 , 38 , 39 ) although a study by Shilts and Wright ( 40 ) has reported no evidence for CD147 as a direct SARS-CoV-2 spike binding receptor. The CD147 belongs to the immunoglobulin superfamily and has been reported to be a highly glycosylated trans-membrane protein ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

et al. 2021

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Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.

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“…Basigin's role as SARS-CoV-2 receptor for viral entry is being debated (Figure 4). However, in silco and molecular dynamic simulation studies provide evidence that T lymphocytes, which do not appear to express ACE2 [136], strongly interact through C-terminal domain of basigin with Arg403, Asn481 and Gly502 of the SARS-CoV-2 spike protein [161]. However, the tropism of SARS-CoV-2 to lung alveolar epithelium does not match the tissue expression…”

Section: Role Of Basigin In Covid-19mentioning

confidence: 99%

ACE2: from protection of liver disease to propagation of COVID-19

et al. 2020

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Twenty years ago, the discovery of angiotensin-converting enzyme 2 (ACE2) was an important breakthrough dramatically enhancing our understanding of the renin–angiotensin system (RAS). The classical RAS is driven by its key enzyme ACE and is pivotal in the regulation of blood pressure and fluid homeostasis. More recently, it has been recognised that the protective RAS regulated by ACE2 counterbalances many of the deleterious effects of the classical RAS. Studies in murine models demonstrated that manipulating the protective RAS can dramatically alter many diseases including liver disease. Liver-specific overexpression of ACE2 in mice with liver fibrosis has proved to be highly effective in antagonising liver injury and fibrosis progression. Importantly, despite its highly protective role in disease pathogenesis, ACE2 is hijacked by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans. COVID-19 is frequently life-threatening especially in elderly or people with other medical conditions. As an unprecedented number of COVID-19 patients have been affected globally, there is an urgent need to discover novel therapeutics targeting the interaction between the SARS-CoV-2 spike protein and ACE2. Understanding the role of ACE2 in physiology, pathobiology and as a cellular receptor for SARS-CoV-2 infection provides insight into potential new therapeutic strategies aiming to prevent SARS-CoV-2 infection related tissue injury. This review outlines the role of the RAS with a strong focus on ACE2-driven protective RAS in liver disease and provides therapeutic approaches to develop strategies to prevent SARS-CoV-2 infection in humans.

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Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

Cited by 78 publications

References 93 publications

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

ACE2: from protection of liver disease to propagation of COVID-19

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