L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.

Distinctive Roles of Furin and TMPRSS2 in SARS-CoV-2 Infectivity

“…Consistent with previous data ( 19 , 29 , 44 , 54 ), processing at S1/S2 is required for optimal viral entry in Calu-3 lung epithelial cells. Indeed, mutation of the arginines in the FCS or blocking S1/S2 cleavage by a series of novel furin inhibitors effectively reduced SARS-CoV-2 entry in Calu-3 cells.…”

“…High-quality plaque pictures were taken using a high-resolution DLSR camera (Nikon; model D80; objective, AF Micro-Nikkor 60 mm f/2.8D). Plaques were counted manually and in parallel, imaged plaque plates were processed, and plaques were enumerated using an automated algorithm-based Matlab software, as previously reported ( 54 ). In brief, the program assigned a color to every object and each individual plaque was arbitrarily given a color shade, while fused plaques received one single color.…”

Integration Analysis of Pharmacokinetics and Metabolomics to Predict Metabolic Phenotype and Drug Exposure of Remdesivir

“…It is reported that carnitines play a crucial role in the viral infection process. Bellamine et al ( Bellamine et al, 2021 ) revealed that l -carnitine tartrate supplementation in humans and rodents led to a significant decrease in angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2, and Furin, which are in charge of viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Pretesting carnitine is necessary possibly to limit SARS-CoV-2 infection.…”

COVID‐19 and varicocele: The possible overlap factors and the common therapeutic approaches

“…In addition, glutathione, glutathione peroxidase, superoxide dismutase, and catalase activities were significantly lower among the COVID-19 patients than in the control group. 132 Literature reviews suggested that some antioxidant like melatonin, 133 zinc, 134 vitamin C, 135 glutathione, 136 L-carnitine, 137 honey, 138 selenium, 130 silymarin, 139 astaxanthin, 140 quercetin, 141 and pentoxifylline 142 may provide beneficial and supportive treatments against COVID-19 infection by anti-apoptotic, anti-viral, and anti-inflammatory properties.…”

“…Among them, selenium, silymarin, L-carnitine, and honey inhibit viral attachment, fusion, and entry into the host cells. 130,[137][138][139] Therefore, the administration of antioxidants as adjutants has the potential to be a supportive treatment in varicocele patients with COVID-19.…”