Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19.

Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.

Effect of adsorbed polyelectrolytes on nanoscale zero valent iron particle attachment to soil surface models.

Polyelectrolyte coatings significantly increase the mobility of nanoscale zerovalent iron (NZVI) in saturated porous media. The effect can be attributed to improved colloidal stability of NZVI suspensions, decreased adhesion to soil surfaces, or a combination of the two effects. This research explicitly examines how coatings control NZVI adhesion to model soil surfaces. NZVI was coated with three different polyeleotrolyte block copolymers based on poly(methacrylic acid), poly(methyl methacrylate or butyl methacrylate), and poly(styrenesulfonate) or with a poly(styrenesulfonate) homopolymer. SiO2 and a humic acid film served as model soil surfaces. The polyelectrolytes increased the magnitude of the electrophoretic mobility of NZVI over a broad pH range relative to unmodified NZVI and shifted the isoelectric point outside the typical groundwater pH range. Quartz crystal microgravimetry measurements indicated extensive adhesion of unmodified NZVI to SiO2. Polyelectrolyte coatings decreased adhesion by approximately 3 orders of magnitude. Adding 50 mM NaCL to screen electrostatic repulsions did not significantly increase adhesion of modified NZVI. Coated NZVI did not adhere to humic acid films for either 1 mM NaHCO3 or 1 mM NaHCO3 + 50 mM NaCl. The lack of adhesion even in a high ionic strength medium was attributed to electrosteric repulsion, as opposed to electrostatic double layer repulsion, between the polyelectrolyte-coated NZVI and the negatively charged surfaces. The lack of significant adhesion on either model surface was observed for all polymer architectures investigated.