Kidney Injury Molecule-1 Is an Independent Receptor from ACE2 for SARS-CoV-2 in Lung and Kidney
Bibliographic record
Abstract
Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 continues to contribute to a world-wide pandemic. SARS-CoV-2-associated respiratory failure and acute kidney injury are major complications of infection. KIM-1 is a scavenger receptor expressed by renal epithelial cells and has been reported to be a receptor for several viruses. We hypothesized that KIM-1 is a receptor for SARS-CoV-2 and may play an essential role in COVID-19 lung and kidney injury. Methods: Human lung and kidney autopsy samples were immunostained and analyzed. Uptake of “virosomes”, liposomal nanoparticles displaying the SARS-CoV-2 spike protein, by A549 lung epithelial cells, mouse primary lung epithelial cells, and human kidney tubular organoids was evaluated in the presence or absence of anti-KIM-1 antibody or TW-37, a KIM-1-mediated endocytosis inhibitor. Protein-protein interaction characteristics between purified SARS-CoV-2 spike protein and purified KIM-1 were determined using flow cytometry-based immunoprecipitation. HEK293 cells expressing human KIM-1 but not functional angiotensin-converting enzyme 2 (ACE2), a known receptor, were infected with live SARS-CoV-2. ACE2 complete knockout HEK293 cells were produced and exposed to the SARS-CoV-2 spike protein. Results: KIM-1 was expressed in lung and kidney epithelial cells in COVID-19 patient samples. Human and mouse lung and kidney epithelial cells expressed KIM-1 and endocytosed spike-virosomes. Both anti-KIM-1 antibodies and TW-37 inhibited uptake. Enhanced KIM-1 expression in human kidney tubular organoids increased virosome uptake. Purified SARS-CoV-2 spike protein and KIM-1 bound to each other and TW-37 inhibited the binding. KIM-1-expressing HEK293 cells without functional ACE2 expression had increased susceptibility to infection by live SARS-CoV-2 when compared with control cells. KIM-1-expressing ACE2 knockout HEK293 cells internalized SARS-CoV-2 spike protein. Conclusions: KIM-1 is an independent receptor from ACE2 for SARS-CoV-2 in the lung and kidney based on ACE2 knockout cell condition. TW-37 can be potential therapeutic agent and/or prophylactic agent for COVID-19. Funding: NIDDK Support, Commercial Support - Bayer Yakuhin Ltd., Private Foundation Support, Government Support - Non-U.S.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".