Targeting papillomavirus infections: high-throughput screening reveals an effective inhibitor of cutaneous β-HPV types

Abstract

Human papillomaviruses (HPVs) are linked to various cancers of the skin and mucous membranes. While vaccines exist for some mucosal HPV types, they are ineffective against skin-infecting variants and cannot treat existing infections. This highlights the urgent need for HPV-specific antiviral drugs. In this study, we identified a promising lead compound, 5,7-dimethoxy-2-pyridin-3-ylchromen-4-one (NSC51349), through high-throughput screening of the Diversity Set VI library of small molecules. NSC51349 inhibits the replication of HPV5, a cancer-associated skin virus, in human cells without affecting cell viability, growth, or differentiation. It also inhibits the replication of other cutaneous HPV types, including HPV8 and HPV38, further supporting its broad potential. NSC51349 targets the viral protein E2, which is crucial for HPV replication. By binding to specific regions of E2, it interferes with its transcriptional activity, halting viral replication and the expression of viral oncogenes. This study introduces NSC51349 as a strong candidate for antiviral drug development.