Antiviral activities of sulfonium-ion glucosidase inhibitors and 5-thiomannosylamine disaccharide derivatives against dengue virus

Mohan, Sankar; McAtamney, Sarah; Jayakanthan, Kumarasamy; Eskandari, Razieh; Itzstein, Mark von; Pinto, B. Mario

doi:10.1016/j.ijantimicag.2012.05.002

Cited by 7 publications

(2 citation statements)

References 14 publications

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“…At this point, NS1 reaches chaperones to be properly folded and proceed downstream to the Golgi, where a complex glycan is attached to Asn-130 [84,85]. Several antiviral studies using compounds that block ER glucosidases have shown promising results in virus-infected animals to reduce mortality, viremia, and viral RNA levels [86][87][88][89][90]. A couple of caveats to these studies are that the majority are only tested in response to DENV infections, and the safety and efficacy has not been proven in humans.…”

Section: Importance Of Adding Carbohydratesmentioning

confidence: 99%

Flavivirus NS1 and Its Potential in Vaccine Development

Carpio

Barrett

2021

Vaccines

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The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure–function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.

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Section: Importance Of Adding Carbohydratesmentioning

confidence: 99%

Flavivirus NS1 and Its Potential in Vaccine Development

Carpio

Barrett

2021

Vaccines

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“…Separate studies also reported additional classes of α-glucosidase with antiviral roles against DENV. It was shown that the sulfonium-ion α-glucosidase inhibitors kotalanol and its de-O-sulfonated derivative can also interfere with DENV infection [94]. The α-glucosidase substrate mimics CM-9-78 and CM-10-18 were also found to efficiently inhibit DENV infection in vitro , and reduce viremina as well as DENV infection induced disease and death in mice [97,98].…”

Section: A Summary Of the Current State Of Anti-flaviviral Therapementioning

confidence: 99%

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

Krishnan

García-Blanco

2014

Viruses

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West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

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