'''Celgosivir''', in development by Migenix for the treatment of [[hepatitis C virus]] (HCV) infection, is an oral [[prodrug]] of the natural product [[castanospermine]] that inhibits [[alpha-glucosidase]] I, an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked [[oligosaccharides]] of viral envelope [[glycoproteins]]. Celgosivir is well absorbed ''[[in vitro]]'' and ''[[in vivo]]'', and is rapidly converted to castanospermine. Celgosivir has a novel [[mechanism of action]] (preventing the glycosylation of viral proteins by the host), and demonstrates broad antiviral activity ''in vitro''.<ref name=Durantel>{{cite journal | pmid=19649930 | year=2009 | author1=Durantel | first1=D | title=Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection | journal=Current Opinion in Investigational Drugs | volume=10 | issue=8 | pages=860–70 }}</ref>
[[File:Celgosivir.svg|thumb|right|Chemical structure of Celgosivir]]
==Clinical trials==
'''Celgosivir''' is an investigational antiviral drug that has been studied for its potential use in treating infections caused by [[flavivirus]]es, such as [[dengue fever]]. It is a prodrug of [[castanospermine]], a natural compound that inhibits the enzyme [[_-glucosidase I]], which is involved in the processing of viral glycoproteins.
Celgosivir is not efficient as a monotherapy for the treatment of HCV, but has demonstrated a synergistic effect in combination with [[pegylated interferon alfa-2b]] plus [[ribavirin]], both ''in vitro'' and in phase II clinical trials that last up to 1 year in patients with chronic HCV infection. Celgosivir may prove to be a valuable component for combination therapy and may help to prevent the apparition of drug resistance. Long-term toxicity studies are necessary to confirm the safety of celgosivir in humans.<ref name=Durantel/>
Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with [[dengue fever]].<ref>{{cite journal | doi = 10.1016/S1473-3099(14)70730-3| pmid = 24877997| title = Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): A phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial| journal = The Lancet Infectious Diseases| volume = 14| issue = 8| pages = 706| year = 2014| last1 = Low| first1 = Jenny G| last2 = Sung| first2 = Cynthia| last3 = Wijaya| first3 = Limin| last4 = Wei| first4 = Yuan| last5 = Rathore| first5 = Abhay P S| last6 = Watanabe| first6 = Satoru| last7 = Tan| first7 = Boon Hian| last8 = Toh| first8 = Liying| last9 = Chua| first9 = Lian Tee| last10 = Hou| first10 = Yan'an| last11 = Chow| first11 = Angelia| last12 = Howe| first12 = Shiqin| last13 = Chan| first13 = Wing Ki| last14 = Tan| first14 = Kah Hin| last15 = Chung| first15 = Jasmine S| last16 = Cherng| first16 = Benjamin P| last17 = Lye| first17 = David C| last18 = Tambayah| first18 = Paul A| last19 = Ng| first19 = Lee Ching| last20 = Connolly| first20 = John| last21 = Hibberd| first21 = Martin L| last22 = Leo| first22 = Yee Sin| last23 = Cheung| first23 = Yin Bun| last24 = Ooi| first24 = Eng Eong| last25 = Vasudevan| first25 = Subhash G}}</ref>
== Mechanism of Action ==
==References==
Celgosivir works by inhibiting the host cell enzyme [[_-glucosidase I]], which is crucial for the proper folding and maturation of viral glycoproteins. By blocking this enzyme, celgosivir disrupts the assembly and secretion of infectious viral particles. This mechanism is particularly effective against viruses that rely heavily on glycoprotein processing, such as the [[dengue virus]].
Celgosivir has undergone several phases of clinical trials to evaluate its safety and efficacy in treating [[dengue fever]]. Early studies have shown that celgosivir can reduce viral load and improve clinical outcomes in patients with dengue. However, further research is needed to fully establish its therapeutic potential and to determine the optimal dosing regimen.
[[Category:Iminosugars]]
[[Category:Butyrate esters]]
== Potential Applications ==
[[Category:Triols]]
[[Category:Indolizidines]]
While primarily studied for [[dengue fever]], celgosivir's mechanism of action suggests it could be effective against other [[flavivirus]]es, including [[West Nile virus]], [[yellow fever virus]], and [[Zika virus]]. Its broad-spectrum antiviral activity makes it a promising candidate for further development in the fight against emerging viral infections.
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== Challenges and Considerations ==
One of the main challenges in developing celgosivir as a therapeutic agent is its potential toxicity and side effects, which need to be carefully balanced against its antiviral benefits. Additionally, the development of resistance and the variability in response among different patient populations are important considerations in its clinical application.
Celgosivir is an investigational antiviral drug that has been studied for its potential use in treating infections caused by flaviviruses, such as dengue fever. It is a prodrug of castanospermine, a natural compound that inhibits the enzyme _-glucosidase I, which is involved in the processing of viral glycoproteins.
Celgosivir works by inhibiting the host cell enzyme _-glucosidase I, which is crucial for the proper folding and maturation of viral glycoproteins. By blocking this enzyme, celgosivir disrupts the assembly and secretion of infectious viral particles. This mechanism is particularly effective against viruses that rely heavily on glycoprotein processing, such as the dengue virus.
Celgosivir has undergone several phases of clinical trials to evaluate its safety and efficacy in treating dengue fever. Early studies have shown that celgosivir can reduce viral load and improve clinical outcomes in patients with dengue. However, further research is needed to fully establish its therapeutic potential and to determine the optimal dosing regimen.
While primarily studied for dengue fever, celgosivir's mechanism of action suggests it could be effective against other flaviviruses, including West Nile virus, yellow fever virus, and Zika virus. Its broad-spectrum antiviral activity makes it a promising candidate for further development in the fight against emerging viral infections.
One of the main challenges in developing celgosivir as a therapeutic agent is its potential toxicity and side effects, which need to be carefully balanced against its antiviral benefits. Additionally, the development of resistance and the variability in response among different patient populations are important considerations in its clinical application.
