Suppression of poxvirus replication by SC144.

Poxviruses are a significant threat to the health of human and economically important animals. Although smallpox, one of the most devastating infectious diseases, is eradicated, the rapid rise of mpox and other poxviral diseases call for the development of antivirals. Here, we show that SC144, a reported small molecule inhibitor of cellular gp130 pathway, suppresses the replication of monkeypox, cowpox, and vaccinia viruses in cultured cells. Interestingly, SC144 likely suppresses vaccinia virus replication independent of gp130. We further show that this suppression of poxvirus replication is achieved by inhibiting viral DNA replication. With EC50 in sub-micromolar range and CC50 of over 250 μM, SC144 is potent and selective, making it a promising candidate for further development as an antiviral against poxviruses.