Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Abstract

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.

Novel Butenolide Derivatives as Dual-Chitinase Inhibitors to Arrest the Growth and Development of the Asian Corn Borer

“…The discovery of flupyradifurone as a commercial insecticide was inspired by the butenolide scaffold of the natural product stemofoline . Compounds containing a butenolide scaffold exhibit broad-spectrum bioactivities, such as antibacterial, In addition antifungal, antiviral, , antitumor, and anti-inflammatory activities, , especially insecticidal activity . Moreover, both furan and benzene moieties are pharmacophores that may aid in the discovery of novel drugs or agrochemicals with antitumor, insecticidal, antifugal, or herbicidal activities .…”

Antimicrobial Activity of Lactones

“…Thanks to this diversity, it is an extremely interesting group that exhibits several important biological properties. Among these activities, the most frequently mentioned are cytotoxic [ 12 , 13 , 14 ], anti-inflammatory [ 15 , 16 ], antiplasmodial [ 17 ], antiviral [ 18 ], and antibacterial. Therefore, a wide selection of articles provides an overview of those biological properties or most often presents, in detail, the anticancer properties [ 4 , 5 , 9 , 19 ].…”