Ocular Surface Expression of SARS-CoV-2 Receptors

Leonardi, Andrea; Rosani, Umberto; Brun, Paola

doi:10.1080/09273948.2020.1772314

Cited by 80 publications

(88 citation statements)

References 25 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 claimed viral receptors with variable qualities of data behind them 9,[32][33][34][35] . We investigated one of the most prominent claims among these, 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 8,14,15,[36][37][38][39] . 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%

“…Basigin represents an attractive medical target because therapeutic agents have already been developed that target basigin based on basigin's previously-established role as an essential host receptor for invasion of the malaria parasite Plasmodium falciparum 11,12 . The claim that basigin acts as a host receptor for SARS-CoV-2 has already featured in published articles discussing the prioritization of therapeutics 13 , and has been the subject of published analyses looking at basigin expression on the assumption that it serves as a viral entry factor [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

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

Shilts

Wright

2020

Preprint

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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 of the role of this host receptor in viral infection and pathogenesis. We sought to independently characterize the basigin-spike protein interaction. After conducting several lines of experiments, we report that we are unable to find evidence supporting the role of basigin as a putative spike-binding receptor. Recombinant forms of both the entire ectodomain and S1 domain of the SARS-CoV-2 spike protein that directly bind ACE2 do not interact with basigin expressed on the surface of human cells. Using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for direct binding of the viral spike to either of the two common isoforms of basigin. Given the pressing need for clarity on which targets of SARS-CoV-2 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%

Section: Introductionmentioning

confidence: 99%

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

Shilts

Wright

2020

Preprint

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“…48 Leonardi et al used RNAseq and microarray to study 18 healthy conjunctival samples and 6 ex vivo healthy cornea samples. 49 They found weak ACE2 expression and intermediate TMPRSS2 expression in the conjunctiva and cornea.…”

Section: The Potential Of Contracting Sars-cov-2 Via the Eyementioning

confidence: 97%

“…In contrast to the cornea, current studies showed that the expression of ACE2 in the conjunctiva is low. [47][48][49] Lange et al used RNA sequencing (RNAseq) to determine ACE2 in 38 conjunctival samples from 38 patients. 47 The authors found no substantial expression of ACE2 or other co-receptors (TMPRSS2, ANPEP, DPP4, and ENPEP) at mRNA levels in conjunctival samples.…”

Section: The Potential Of Contracting Sars-cov-2 Via the Eyementioning

confidence: 99%

<p>The Role of the Ocular Tissue in SARS-CoV-2 Transmission</p>

Peng¹,

Dai²,

Sugali³

et al. 2020

OPTH

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The current global pandemic of coronavirus disease 2019 (COVID-19) has affected over 21 million people and caused over half a million deaths within a few months. COVID-19 has become one of the most severe public health crises in recent years. Compared to other pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly infectious. Due to the lack of specific and effective treatment or vaccines, disease prevention and early detection are essential for establishing guidelines to mitigate further spread. The potential role of the ocular system in COVID-19 is still not clear but it has gained increasing attention. Here, we reviewed both clinical and research evidence on the ocular manifestations associated with COVID-19, the presence of SARS-CoV-2 in ocular surface tissues and tears, and the potential role of the eye in contracting SARS-CoV-2.

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“…It is important to note that this proposed pathway of infection is in no way canonical. For example, recent evidence suggests that Angiotensin II Receptor type 2 (AGTR) is a putative receptor for the virus [ 5 ].…”

Section: What Are the Molecular Mechanisms By Which The Sars-cov-2mentioning

confidence: 99%

Potential of Ocular Transmission of SARS-CoV-2: A Review

Barnett

Wahlin

Krawczyk

et al. 2020

Vision

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Purpose of review: to provide a prospective on the current mechanisms by which SARS-CoV-2 enters cells and replicates, and its implications for ocular transmission. The literature was analyzed to understand ocular transmission as well as molecular mechanisms by which SARS-CoV-2 enters cells and replicates. Analysis of gene expression profiles from available datasets, published immunohistochemistry, as well as current literature was reviewed, to assess the likelihood that ocular inoculation of SARS-CoV-2 results in systemic infection. Recent findings: The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2. In addition to direct ocular infection, virus carried by tears through the nasolacrimal duct to nasal epithelium represent a means of ocular inoculation. Summary: There is evidence that SARS-CoV-2 may either directly infect cells on the ocular surface, or virus can be carried by tears through the nasolacrimal duct to infect the nasal or gastrointestinal epithelium.

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Ocular Surface Expression of SARS-CoV-2 Receptors

Cited by 80 publications

References 25 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

<p>The Role of the Ocular Tissue in SARS-CoV-2 Transmission</p>

Potential of Ocular Transmission of SARS-CoV-2: A Review

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