The synthesis and biological evaluation of lactose-based sialylmimetics as inhibitors of rotaviral infection

Insight into Host Cell Carbohydrate-recognition by Human and Porcine Rotavirus from Crystal Structures of the Virion Spike Associated Carbohydrate-binding Domain (VP8*)

“…14 However, it is not known if the VP8* of any sialidaseinsensitive rotavirus is able to bind carbohydrates, and if so whether recognition of sialic acids occur. As part of our on-going interest in the discovery of novel anti-rotaviral drugs 15,16 and to determine the molecular basis for differences in sialic acid recognition between rotaviruses, we have solved the X-ray structures of VP8* from CRW-8 and Wa crystallised in the presence of the sialic acid derivative methyl α-D-N-acetylneuraminide (Neu5Acα2Me), at 2.3 Å and 2.5 Å resolution, respectively. These structures and comparison with those VP8* from the sialidasesensitive RRV 12 and sialidase-insensitive DS-1 17 provide insight into the remarkable host-specificity that rotavirus exhibit, also indicating how different affinities for the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are attained by the sialidase-sensitive CRW-8 and RRV rotaviruses.…”

Novel Probiotic Bifidobacterium longum subsp. infantis CECT 7210 Strain Active against Rotavirus Infections

“…Specifically, in the European region rotavirus infection causes an estimated 6,550 deaths and 146,287 hospital admissions each year in children under 5 years of age. The average percentages of diarrheal disease admissions attributable to rotavirus have been estimated at 26.4% (low-income countries), 21.3% (lower-middle-income countries), 31.7% (upper-middle-income countries), and 39.5% (high-income countries) (51).…”

“…These studies included different probiotic strains, like Bifidobacterium bifidum and Streptococcus thermophilus (43), Lactobacillus paracasei (45), Lactobacillus rhamnosus GG (23,36), and the probiotic mixture VSL3 (11). Although direct effects have been reported for the addition of different products, such as isoflavones from soy (1), lactose-based sialyl mimetics (31), and medicinal plants (21), on the inhibition of rotavirus replication, to our knowledge there are very few in vivo data that clearly demonstrate the capacity of a probiotic or a probiotic metabolite to inhibit rotavirus infection. In fact, for all the previously reported cases, the protection mechanisms remain unclear.…”

A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

“…In the present study we have investigated the capacity of this synthetase to recognize mimics of CMP-sialic acids in which the main sialic acid pyranose framework is replaced with simple α-linked carboxylic acids and lipophilic functionalities. In a number of sialic acidrecognising protein systems it has been suggested that only the carboxyl group plays a significant role in substrate recognition [3,26]. We have explored two such CMP-sialic acid mimetics, 8a that contains a phenyl group as the lipophilic moiety, and 8b that incorporates a methyl group, and their capacity to be recognized by the CMP-Kdn synthetase.…”

“…We have previously shown that compounds which mimic sialic acids are useful probes in the identification of substrate or product sub-structural binding requirements of sialic acid-recognising proteins [3,25,26]. Therefore, we thought it of value to investigate such binding requirements of the nucleotide CMP-Kdn synthetase through the evaluation of selected sialylnucleoside mimetics (8a and 8b).…”