Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation.

Patients previously infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may experience post-acute adverse health outcomes, known as long COVID. The most reported symptoms are fatigue, headache and attention/concentration issues, dyspnea and myalgia. In addition, reduced aerobic capacity has been demonstrated in both mild and moderate COVID-19 patients. It is unknown whether COVID-19 vaccination mitigates against reduced aerobic capacity. Our aim was to compare the aerobic capacity of vaccinated and unvaccinated individuals previously infected with SARS-CoV-2. Methods: Individuals aged 18 to 65 years with laboratory-confirmed mild to moderate COVID-19 disease were invited to Ziv Medical Centre, Israel, three months after SARS-CoV-2 infection. We compared individuals unvaccinated at the time of infection to those vaccinated in terms of aerobic capacity, measured using symptom-limited cardiopulmonary exercise test (CPET). Results: We recruited 28 unvaccinated and 22 vaccinated patients. There were no differences in baseline demographic and pulmonary function testing (PFT) parameters. Compared with unvaccinated individuals, those vaccinated had higher V’O₂/kg at peak exercise and at the anaerobic threshold. The V’O₂/kg peak in the unvaccinated group was 83% of predicted vs. 100% in the vaccinated (p < 0.002). At the anaerobic threshold (AT), vaccinated individuals had a higher V’O₂/kg than those unvaccinated. Conclusions: Vaccinated individuals had significantly better exercise performance. Compared with vaccinated individuals, a higher proportion of those unvaccinated performed substantially worse than expected on CPET. These results suggest that vaccination at the time of infection is associated with better aerobic capacity following SARS-CoV-2 infection.