Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial.

Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p = 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.

Lessons from an international trial evaluating vaccination strategies for recovered inpatients with COVID-19 (VATICO).

The protection provided by natural versus hybrid immunity from COVID-19 is unclear. We reflect on the challenges from trying to conduct a randomized post-SARS-CoV-2 infection vaccination trial study with rapidly evolving scientific data, vaccination guidelines, varying international policies, difficulties with vaccine availability, vaccine hesitancy, and a constantly evolving virus.

Utilization of Ficus carica leaves as a heterogeneous catalyst for production of biodiesel from waste cooking oil.

Biodiesel appears to be a possible substitute for non-renewable fossil fuels; however, its production requires the presence of a catalyst to accelerate the reaction. Serving the purpose of finding effective, cheap and environmentally safe, heterogeneous catalysts, this research used the fig leaves in three different forms, calcined, activated by KOH, and activated by both K2CO3 and CaCO3. Their efficiency in biodiesel synthesis, from spent cooking oil, was examined and compared with that of activated carbon which has been previously investigated. The properties of different catalyst forms were specified using X-ray diffraction, scanning electron microscope and Fourier transform infrared spectroscopy. Operating parameters studied for the three catalysts were reaction time (from 30 to 180 min), alcohol-to-oil molar ratio (from 4:1 to 10:1), catalyst loading (from 0.5 to 5% by wt.), and stirring speed (from 100 to 400 rpm). The increase in reaction time, molar ratio, and catalyst loading proved to have a favorable effect on % conversion to biodiesel but to a certain degree; increasing the stirring speed augmented the conversion. At optimum conditions (2 h of heating, 6:1 alcohol-to-oil molar ratio, 1% by wt. catalyst loading, and 400 rpm stirring), fig leaves activated by KOH provided the highest conversion to biodiesel (92.73%). The measured properties of the produced biodiesel (density, viscosity, flash point, cloud point, and pour point) yielded encouraging results. Graphical Abstract.