Cholesterol Metabolism—Impacts on SARS-CoV-2 Infection Prognosis

Abstract

The recently emerged pathogenic SARS-coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global pandemic. In this study, we show that SARS-CoV-2 infection was associated with clinically significant lower level of HDL cholesterol (HDL-C), which can be used as indicators of disease severity and poor prognosis. Importantly, we found the spike protein of SARS-CoV-2 (SARS-2-S) bound to HDL. Antagonists of HDL receptor-Scavenger receptor class B type I (SR-B1), strongly inhibited SARS-CoV-2 infection. Notably, the lipids transfer function of SR-B1 was indispensable for this inhibition, offering explanations for the reduced serum HDL level observed in COVID-19 patients. Basing on findings here, we speculate that SR-B1-mediated pulmonary HDL-vitamin E uptake could participate in mediating SARS-CoV-2 infection of lung cells, and the unique expression profile of SR-B1 may also affect SARS-CoV-2 cell and tissue tropism. These findings might help to provide further insights into viral transmission, pathological characteristics and reveal therapeutic targets.

Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study

“…Serum HDL-C levels might decrease and serum total cholesterol/HDL-C ratios might increase proportionally in community-acquired pneumonia [17]. According to Wei C's [18] study, the spike protein of SARS-CoV-2 bound to HDL and antagonists of HDL receptor-Scavenger receptor class B type I inhibited SARS-CoV-2 infection. The lipids transfer function of Scavenger receptor class B type I was indispensable for this inhibition, providing explanations for the reduced serum HDL level in patients with COVID-19.…”

Urine Proteome of COVID-19 Patients

“…Additionally, the down-regulated pathway of lipid metabolic and transport in the COVID-19 patients caused our attention. The cholesterol homeostasis was reported to impact COVID-19 prognosis, virus entry and the antiviral therapies [31]. In our data, the lipid metabolism and transporting, including the cholesterol homeostasis, were down-regulated in the S-COVID ( Figure 5D and Table S5).…”

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

“…It would be worth exploring the lipidomics of SARS-CoV-2 to investigate whether the virus possesses any singularity in terms of composition which can be exploited in its control. A recent retrospective analysis of 861 patients with clinically classified mild, moderate, severe or critical (the latter with respiratory failure, shock or organ failure) COVID-19 analyzed the possible association with plasma cholesterol and HDL on morbidity and prognosis (Wei et al 2020). The levels of total cholesterol and HDL were found to be inversely correlated with the severity of the disease, and severely ill patients with high HDL had a better prognosis.…”

“…Survivors also had higher cholesterol and HDL levels. Furthermore, pretreatment with ITX 5061, a potent antagonist of SR-B1 that increases HDL levels, competitively inhibited infection of HEX-293T by the virus (Wei et al 2020), thus providing another avenue of possible prophylactic intervention. Interestingly, these authors analyzed the sequences of SARS-CoV-proteins and found the presence of 6 cholesterol recognition motifs like the ones we have described in membrane proteins (Fantini and Barrantes 2013), including the adjacent mirror CARC-CRAC motif (Fantini et al 2016).…”