Single-Molecule Analysis of SARS-CoV-2 Binding to C-Type Lectin Receptors.

Despite intense scrutiny throughout the pandemic, development of efficacious drugs against SARS-CoV-2 spread remains hindered. Understanding the underlying mechanisms of viral infection is fundamental for developing novel treatments. While angiotensin converting enzyme 2 (ACE2) is accepted as the key entry receptor of the virus, other infection mechanisms exist. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and its counterpart DC-SIGN-related (DC-SIGNR, also known as L-SIGN) have been recognized as possessing functional roles in COVID-19 disease and binding to SARS-CoV-2 has been demonstrated previously with ensemble and qualitative techniques. Here we examine the thermodynamic and kinetic parameters of the ligand-receptor interaction between these C-type lectins and the SARS-CoV-2 S1 protein using force-distance curve-based AFM and biolayer interferometry. We evidence that the S1 receptor binding domain is likely involved in this bond formation. Further, we employed deglycosidases and examined a nonglycosylated S1 variant to confirm the significance of glycosylation in this interaction. We demonstrate that the high affinity interactions observed occur through a mechanism distinct from that of ACE2.

Vitamin D status among patients with drug-resistant and non-drug-resistant epilepsy.

Background & Aims: Epilepsy affects nearly 70 million people worldwide. Vitamin D deficiency may influence the balance of certain epilepsies. The purpose of this study was to determine the vitamin D status and anthropometric measurements of people with epilepsy (PWE), according to their pharmacosensitivity. Methods: Forty-six PWE, with or without drug resistance, underwent nutritional assessment after giving consent. Weight, body mass index (BMI), triceps skinfold thickness (TSF), fat mass (FM) and free fat mass (FFM) by bioelectrical impedance analysis were measured. Serum vitamin D was determined without supplementation. Deficiency was defined as a level < 30 ng/mL. Statistical analysis involved Student t test, ANOVA and Chi2. Results: Patients were aged 44.5 ± 14.3 years, with 60.9% of drug-resistance. BMI was 28.7 ± 7.0, 2.2% were malnourished and 30.4% obese according to the BMI. The average vitamin D level was 15.3 ± 9.9 ng/mL, with 87.0% of deficiency, and 40.0% of severe deficiency (<10 ng/mL). The TSF was higher in drug-resistant cases (p = 0.03). There was no link between drug resistance and anthropometric measurements, FM, FFM or vitamin D concentration. Conclusions: Although limited in size, this study showed that PWE are more often obese. Vitamin D deficiency is more common than in the general population, with a much higher prevalence of severe deficiency.