Estimating the in vivo prophylactic effect of mosnodenvir, a novel dengue antiviral, on DENV-2 infection

Almost half of the world's population is at risk of acquiring dengue virus (DENV) each year. However, no specific licensed prophylactic or antiviral treatment for dengue currently exists. Mosnodenvir, a novel DENV inhibitor, has been shown to inhibit DENV replication in vitro and in animal studies. Here, we provide new insights into the in vivo prophylactic inhibitory effect of mosnodenvir exposure on primary DENV-2 infection by fitting mechanistic within-host models of DENV infection to virological and serological data observed from pre-clinical challenge studies in AG129 mice and rhesus macaques. We estimated a median mosnodenvir concentration achieving 50% of maximal inhibitory effect (IC50) on viral replication of 8.35 (6.82, 9.22) ng ml-1 and 7.61 (5.67, 8.92) ng ml-1 for AG129 mice and rhesus macaques, respectively. A higher concentration is typically required to suppress viral replication in AG129 mice compared with rhesus macaques owing to a higher estimated within-host basic reproduction number (R0) in mice. By integrating multiple data types in a single framework, this study enhances our understanding of the within-host dynamics of primary DENV infection in non-human host species. Furthermore, the methods developed here could possibly assist in quantifying the prophylactic inhibitory effect of mosnodenvir on DENV infections in humans.