Comment from Gillian McCrea

Molnupiravir (Lagevrio) for Long COVID Reaching viral reservoirs that protease inhibitors miss | For FDA repurposing / advisory review The opportunity Antiviral trials in Long COVID have focused on one drug class hitting one compartment. Molnupiravir offers a different mechanism and a different tissue reach — aimed at reservoirs the others leave behind. A complementary mechanism Molnupiravir is an oral RNA-polymerase mutagen that disrupts viral replication by a route entirely distinct from protease inhibitors. Researchers note the gastrointestinal tract is a likely hiding spot for SARS-CoV-2 reservoirs, while protease inhibitors are most effective in the lungs [1] — a gap a second agent can close. It is already authorized Molnupiravir is FDA-authorized for acute COVID-19 with established dosing and manufacturing [2]; it has simply never been evaluated for Long COVID. The ask A biomarker-gated trial — alone or combined with a protease inhibitor — in antigen-positive Long COVID, designed to reach reservoir sites that single-agent, short-course trials could not. The drug is on the shelf; the reservoir biology now tells us where to aim it. Sources 1. GI tract as a likely SARS-CoV-2 reservoir; Paxlovid and Lagevrio differ in tissue penetration (Cherry / PolyBio symposium; The Sick Times, Aug 2025). 2. Molnupiravir (Lagevrio): FDA Emergency Use Authorization for acute COVID-19. 3. STOP-PASC / viral-persistence context motivating reservoir-directed antiviral strategies.