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Scaling the Process Chemistry of a COVID-19 Antiviral Pharmaceutical Down for a Multistep Synthesis Experiment in the Undergraduate Teaching Laboratory

Overview
Journal J Chem Educ
Date 2024 Mar 18
PMID 38495616
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Abstract

Molnupiravir is an orally bioavailable direct acting antiviral agent that received emergency use authorization in late 2021 from the FDA for the treatment of patients with mild, moderate, or severe COVID-19. This prodrug is metabolized into a ribonucleoside that is incorporated into the viral RNA during replication. Its tautomerization between cytidine- and uridine-like forms ultimately causes multiple irreversible errors in the genetic code of the virus, which prevents successful viral replication. There are multiple process chemistry routes for molnupiravir synthesis published in the literature that attempt to maximize synthetic yield while minimizing cost and waste, which are goals similar to those of an implementable educational laboratory experiment for the teaching laboratory. We have developed a multiweek laboratory module for undergraduate students in which students conduct a multistep synthesis of molnupiravir. Specifically, our Organic Chemistry II Laboratory students performed the final two steps of molnupiravir synthesis using procedures derived directly from the published process chemistry literature. We utilized this opportunity to introduce students to reading and interpreting these primary experimental sources. Students obtained authentic characterization data via high pressure liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy to assess the conversion and purity of their products at each synthetic step. We report our in-lab activities and student generated data as well as suggestions for how this laboratory experiment could be tailored to meet similar learning objectives in other courses, such as medicinal chemistry or capstone laboratory courses, and as a function of available instrumentation.

References
1.
Kabinger F, Stiller C, Schmitzova J, Dienemann C, Kokic G, Hillen H . Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021; 28(9):740-746. PMC: 8437801. DOI: 10.1038/s41594-021-00651-0. View

2.
Chang J, Ji Y, Li Y, Pan H, Su P . Prevalence of anxiety symptom and depressive symptom among college students during COVID-19 pandemic: A meta-analysis. J Affect Disord. 2021; 292:242-254. PMC: 8595068. DOI: 10.1016/j.jad.2021.05.109. View

3.
Mazzotta V, Lepri A, Colavita F, Rosati S, Lalle E, Cimaglia C . Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents. J Med Virol. 2022; 95(1):e28186. PMC: 9539310. DOI: 10.1002/jmv.28186. View

4.
Butler C, Hobbs F, Gbinigie O, Rahman N, Hayward G, Richards D . Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2022; 401(10373):281-293. PMC: 9779781. DOI: 10.1016/S0140-6736(22)02597-1. View

5.
Gaizo Moore V, Scheifele L, Chihade J, Provost J, Roecklein-Canfield J, Tsotakos N . COVID-360: A Collaborative Effort to Develop a Multidisciplinary Set of Online Resources for Engaging Teaching on the COVID-19 Pandemic. J Microbiol Biol Educ. 2021; 22(1). PMC: 8012042. DOI: 10.1128/jmbe.v22i1.2623. View