Design and evaluation of novel hydrazide derivatives as NS1 inhibitors for dengue virus: synthesis, experimental, and computational studies

Abstract

The lack of highly effective therapeutics to treat the life threatening disease caused by dengue virus (Denv) has posed several challenges to the human community. The increasing prevalence of dengue infections has demanded advanced strategies for disease surveillance and to accomplish precise diagnosis across all reported serotypes of Denv. A promising combating approach involved the targeted inhibition of specific viral proteins that are involved in the pathogenesis pathway of the virus. With the recently developed advanced strategies of rational drug design and chemical modifications such approaches have been more successful. Further, the efficacy and specificity of the proposed drugs can further be optimized through structure–activity relationship (SAR) evaluations. With the established role of non-structural protein 1 (NS1) of the dengue virus (dNS1) in pathogenesis, herein a few hydrazide-based derivatives were strategically designed to block its functions including replication, immune evasion, endothelial dysfunction, etc. The inhibition of this protein could effectively curb the viral pathogenicity. Moreover, this study explores the rational design and synthesis of novel hydrazide derivatives to target NS1, thereby offering a potential therapeutic intervention against dengue. The findings could contribute to the advancement of antiviral drug development, addressing the urgent need for effective treatment options against dengue infections.