ABSTRACT
SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Chlorocebus aethiops , Humans , Antiviral Agents/pharmacology , Post-Acute COVID-19 Syndrome , Virus Replication , Vero CellsABSTRACT
SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection.Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.
Subject(s)
COVID-19ABSTRACT
The COVID-19 pandemic is ongoing and we are still compiling new findings to decipher and understand SARS-CoV-2 infection during pregnancy. No reports encompass any conclusive confirmation of vertical transmission. Nevertheless, cases of fetal distress and multiple organ failure have been reported, as well as rare cases of fetal demise. While clinicians and scientists continue to seek proof of vertical transmission, they miss the greater point, namely the cause of preterm delivery. In this review, we suggest that the cause might not be due to the viral infection but the fetal exposure to maternal inflammation or cytokine storm that translates into a complication of COVID-19. This statement is extrapolated from previous experience with infections and inflammation which were reported to be fatal by increasing the risk of preterm delivery and causing abnormal neonatal brain development and resulting in neurological disorders like atypical behavioral phenotype or autistic syndrome. Given the potentially fatal consequences on neonate health, we highlight the urgent need for an animal model to study vertical transmission. The preclinical model will allow us to make the link between SARS-COV-2 infection, inflammation and long-term follow-up of child brain development.