Modeling of Molnupiravir Interaction with Interferon

COVID-19 has showcased the need for effective antiviral therapies and a better understanding of therapies' interaction with the immune response in the host. Molnupiravir, a nucleoside analog that induces viral mutagenesis, demonstrates a potential therapeutic approach, but its optimal dosage and deployment may depend on the complex interactions with the interferon (IFN) response. We developed a mathematical model to investigate how various mechanisms of IFN impact molnupiravir efficacy in controlling SARS-CoV-2 infection. Our ordinary differential equation model explicitly tracks target cells, eclipse-phase infected cells, productively infected cells, wild-type virus, mutated virus, and interferon levels. The results display that IFN blocking of viral infection primarily controls early exponential growth, while IFN blocking of viral production reduces overall viral burden. We demonstrate synergistic interactions between both IFN mechanisms of action and molnupiravir, with the strongest viral suppression when dual IFN activity combines with high drug efficacy. These findings suggest that immune responses play an important role in helping suppress infection even in the presence of antiviral treatment.