Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 24;13(5):903-905.
doi: 10.1093/ckj/sfaa193. eCollection 2020 Oct.

Cilastatin: a potential treatment strategy against COVID-19 that may decrease viral replication and protect from the cytokine storm

María Ángeles González-Nicolás  1   2 , Cristian González-Guerrero  1 , Verónica Astrid Pérez-Fernández  1 , Alberto Lázaro  1   3
Affiliations

Cilastatin: a potential treatment strategy against COVID-19 that may decrease viral replication and protect from the cytokine storm

María Ángeles González-Nicolás et al. Clin Kidney J. .
No abstract available

PubMed Disclaimer

Figures

FIGURE 1:
FIGURE 1:
Cilastatin improves bacterial LPS-induced lung injury in vivo. Thirty-six 6-week-old male Wistar rats weighing 150–200 g were administered intraperitoneally with 10 mg/kg LPS from Escherichia coli O55:B5 (Sigma Aldrich, St Louis, MO, USA) or its vehicle (0.9% NaCl) and 150 mg/kg cilastatin (Acs Dobfar, Tribiano, Milan, Italy) or its vehicle (0.9% NaCl) also injected intraperitoneally. The dose of cilastatin was administered just before the administration of LPS, and the rats (n = 9 animals per group) were euthanized within 24 h. Upper row: paraffin-embedded lung sections stained with haematoxylin–eosin (H&E). Control group shows normal lung structure; LPS-injected lungs show severe alveolar wall oedema, congestion, haemorrhage and increased inflammatory cell numbers. These changes were significantly reduced by treatment with cilastatin, with the lungs showing almost normal morphology. Lower row: immunolocalization of CD68 (monocyte/macrophage) in lung sections. Note increased CD68-stained cells in LPS-injected rats compared with the control group (staining score: 17.00 ± 3.50 versus 5.20 ± 1.16; P = 0.0014). Cilastatin significantly reduced the increase of CD68 expression induced by LPS (staining score: 5.50 ± 1.63 versus 17.00 ± 3.50; P = 0.0012). In both cases, treatment with cilastatin alone had no effects on lung morphology or inflammation.
FIGURE 2:
FIGURE 2:
Cilastatin may decrease SARS-CoV-2 replication and cell damage. (A) This represents SARS-CoV-2 infection of kidney/lung epithelium through ACE2 receptor, thus activating Fas/Fas ligand (FasL) trimerization and triggering reactive oxygen species (ROS), inflammation and apoptosis, leading to exponential cytokine storm, cell damage and death. (B) This shows cilastatin as a potential treatment that may prevent SARS-CoV-2 internalization and replication and protect from cell damage by blocking specifically DHP-I enzyme localized in cholesterol lipid rafts of the apical membrane, avoiding Fas/FasL trimerization and diminishing ROS, inflammation, apoptosis and cytokine storm.
See this image and copyright information in PMC

Comment in

References

    1. Rubin S, Orieux A, Prevel R. et al. Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019. Clin Kidney J 2020; 13: 354–361 - PMC - PubMed
    1. Hoffmann M, Simon Schroeder H, Krüger N. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271–280 - PMC - PubMed
    1. Humanes B, Lazaro A, Camano S. et al. Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats. Kidney Int 2012; 82: 652–663 - PubMed
    1. Ortiz-Arduan A, Danoff TM, Kalluri R. et al. Regulation of Fas and Fas ligand expression in cultured murine renal cells and in the kidney during endotoxemia. Am J Physiol 1996; 271: F1193– F1–201. - PubMed
    1. Humanes B, Camaño S, Lara JM. et al. Cisplatin-induced renal inflammation is ameliorated by cilastatin nephroprotection. Nephrol Dial Transplant 2017; 32: 1645–1655 - PMC - PubMed