https://www.researchgate.net/publication/303800170_Discovery_of_prenylated_flavonoids_with_dual_activity_against_influenza_virus_and_Streptococcus_pneumoniae
Abstract
Influenza
virus neuraminidase (NA) is the primary target for influenza
therapeutics. Severe complications are often related to secondary
pneumonia caused by Streptococcus pneumoniae (pneumococci), which also
express NAs. Recently, a NA-mediated lethal synergism between influenza A
viruses and pneumococci was described. Therefore, dual inhibitors of
both viral and bacterial NAs are expected to be advantageous for the
treatment of influenza. We investigated the traditional Chinese herbal
drug sāng bái pí (mulberry root bark) as source for anti-infectives. Two
prenylated flavonoid derivatives, sanggenon G (4) and sanggenol A (5)
inhibited influenza A viral and pneumococcal NAs and, in contrast to the
approved NA inhibitor oseltamivir, also planktonic growth and biofilm
formation of pneumococci. Evaluation of 27 congeners of 5 revealed a
correlation between the degree of prenylation and bioactivity.
Abyssinone-V 4′-methyl ether (27) inhibited pneumococcal NA with IC50 =
2.18 μM, pneumococcal growth with MIC = 5.63 μM, and biofilm formation
with MBIC = 4.21 μM, without harming lung epithelial cells. Compounds 5
and 27 also disrupt the synergism between influenza A virus and
pneumococcal NA in vitro, hence functioning as dual-acting
anti-infectives. The results warrant further studies on whether the
observed disruption of this synergism is transferable to in vivo
systems.
