2022
DOI: 10.1016/j.antiviral.2022.105325
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Nafamostat mesylate as a broad-spectrum candidate for the treatment of flavivirus infections by targeting envelope proteins

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Cited by 14 publications
(6 citation statements)
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“…Briefly, in such a strategy, compounds or drugs that have been studied for a certain therapeutic use would be re-investigated for a different therapeutic purpose. Adopting this method, repurposing of the anticoagulant drug nafamostat ( 1 , Figure 1 ) and the anti-acute pancreatitis camostat ( 2 , Figure 1 ) showed that they can potentially inhibit TMPRSS2-dependent viral entry, and they underwent clinical trials as possible COVID-19 treatments [ 15 , 17 , 43 , 44 , 45 ]. Nevertheless, they suffered drawbacks and limitations that stalled further advancement.…”
Section: Resultsmentioning
confidence: 99%
“…Briefly, in such a strategy, compounds or drugs that have been studied for a certain therapeutic use would be re-investigated for a different therapeutic purpose. Adopting this method, repurposing of the anticoagulant drug nafamostat ( 1 , Figure 1 ) and the anti-acute pancreatitis camostat ( 2 , Figure 1 ) showed that they can potentially inhibit TMPRSS2-dependent viral entry, and they underwent clinical trials as possible COVID-19 treatments [ 15 , 17 , 43 , 44 , 45 ]. Nevertheless, they suffered drawbacks and limitations that stalled further advancement.…”
Section: Resultsmentioning
confidence: 99%
“…Most studies perform molecular docking using only one protein structure, which may not offer the most representative conformation; here, we used 3000 protein frames to evaluate the binding affinity of CA. This substance showed promising inhibition capacity by binding in regions previously studied for potential inhibitive action [ 58 , 59 , 84 ]. Finally, the AutoDock Vina results were better than crystallographic structures with CA acting as an inhibitor.…”
Section: Discussionmentioning
confidence: 99%
“…Ensemble docking in this study was performed using all frames from each MD trajectory (replicate); each trajectory has 1000 frames. Docking analysis was limited to regions (including DI and DIII) reported as active site of the protein important for receptor binding and it has been described as an important target for viral-host fusion reaction [ 58 , 59 , 60 ]. Because we were working with dimeric E protein, two binding pockets (BP) to be docked by CA (molecular docking) were defined in each MD frame from three replicates (3000 frames) (See Figure S1 to observe both BP regions in one frame).…”
Section: Methodsmentioning
confidence: 99%
“…For the virus yield reduction assay, the BHK or Vero cells were seeded in a 12-well plate and cultured overnight, and they were then inoculated with gradient-diluted ALP in the presence of the viruses (multiplicity of infection (MOI) = 0.05). After 72 h of incubation, the cellular RNA was extracted using the RNeasy ® Mini Kit and quantified using qRT-PCR, as previously reported [19]. The viral proteins were visualized using an immunofluorescence assay.…”
Section: In Vitro Antiviral Assaymentioning
confidence: 99%