The Long View on COVID-19 Theranostics and Oral Antivirals: Living with Endemic Disease and Lessons from Molnupiravir

The long view on living with COVID-19 as an endemic disease calls for expanding the planetary health intervention toolbox. We will need a battery of vaccines, small molecule oral antiviral drugs, and biomarkers to forecast antiviral drug efficacy and safety. In this context, theranostics refers to fusion of therapeutics and diagnostics. We examine here emerging pathways to theranostics innovation for COVID-19 oral antiviral drugs, with molnupiravir as a case study. With new virus variants (1) variations in the molnupiravir efficacy target, viral RNA-dependent RNA polymerase, (2) variability in pharmacokinetics and exposure to molnupiravir active moiety in fluids on virus entry points to the host (e.g., saliva, tears, and nasal secretions), (3) variability in transformation from prodrug molnupiravir to its active form, and (4) variability in putative adverse effects on human/host cells, all warrant attention for prospects and challenges vis à vis theranostics innovation for COVID-19 oral antivirals. The emerging lessons from molnupiravar are of interest to future design of COVID-19 theranostic research with other oral antiviral medications. Regulatory agencies, the pharmaceutical industry, research funders, governments, and ministries of health around the world have important stewardship roles to advance the subpopulation level analyses of clinical trial data on oral antiviral drugs for COVID-19. This would remedy the current lag in clinically relevant multiomics theranostics for oral antivirals in the battle against COVID-19.