BuCast (celgosivir) / BioWest Therap - LARVOL DELTA

Natural long-chain fatty acyl solamines from the leaves of Solanum bulbocastanum Dun. show antiseptic properties. (PubMed, Fitoterapia) - "Owing to their structural resemblance to the antiseptic cetylpyridinium chloride, this study aimed to evaluate a fraction of a methanolic S. bulbucastanum leaf extract mainly containing long-chain fatty acyl solamines for potential antiseptic applications...In mammalian cell assays, the fraction mirrored the cytotoxic effect of cetylpyridinium chloride in MTT assay (Fibroblasts: IC50 = 1.2 μg/mL, Vero E6: IC50 = 2.2 μg/mL) and the profile in real time cell analysis, suggesting a comparable mode of action. These findings highlight long-chain fatty acyl solamines as promising candidates for the development as bio-based antiseptics, offering a potential green alternative to conventional agents."

Journal

Machine learning and molecular docking prediction of potential inhibitors against dengue virus. (PubMed, Front Chem) - "While the WHO-approved vaccine, Dengvaxia, and antiviral treatments like Balapiravir and Celgosivir are available, challenges such as drug resistance, reduced efficacy, and high treatment costs persist...It suggests a promising pathway for the rapid identification and development of novel antiviral drugs against DENV. These in silico findings provide a strong foundation for future experimental validations and in-vitro studies aimed at fighting DENV."

Journal • Dengue Fever

The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use. (PubMed, Parasit Vectors) - "Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising..."

Journal • Review • Dengue Fever • Dermatology • Infectious Disease • Ophthalmology

Molecular docking analysis of Adhatoda Vasica withThromboxane A2 receptor (TXA2R) (6IIU) and Antiviral molecules for possible dengue complications. (PubMed, Infect Disord Drug Targets) - "The docking was carried out on different ligands like vasicine, ramatroban, Chloroquine, Celgosivir and standard elthrombopag downloaded from the PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Conclusion Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary and it indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue and experimental evaluation will be carried out in near future."

Journal • Dengue Fever • Hematological Disorders • Thrombocytopenia

Murine models of dengue virus infection for novel drug discovery. (PubMed, Expert Opin Drug Discov) - "In fact, the AG129 mouse model allowed the identification of celgosivir, an inhibitor of cellular glucosidases, as a promising option for DENV therapy. However, clinical trials still were not successful, emphasizing the difficulties in the transition from preclinical testing to human treatment."

Journal • Preclinical • Dengue Fever • Infectious Disease • IFNA1

A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19. (PubMed, Sci Rep) - "Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as Propylthiouracil, 2-Bromopalmitate, Lipofermata, Tunicamycin, Benzyl Isothiocyanate, Tipifarnib and Lonafarnib) are also proposed."

Journal • Dengue Fever • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • ACSL3

Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2. (PubMed, Viruses) - "The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19."

Journal • Gaucher Disease • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The iminosugars celgosivir, castanospermine and UV-4 inhibit SARS-CoV-2 replication. (PubMed, Glycobiology) - "The monocyclic UV-4 also prevented SARS-CoV-2-induced death and reduced viral replication after 24 hours of treatment, although the reduction in viral copies was lost after 48 hours. Our findings suggest that iminosugars should be urgently investigated as potential SARS-CoV-2 inhibitors."

Journal • Infectious Disease • Novel Coronavirus Disease

A Dengue type 2 reporter virus assay amenable to high-throughput screening. (PubMed, Antiviral Res) - "To validate the image-based antiviral assay, a panel of reference compounds with different molecular mechanisms of anti-DV activity was assessed: (i) the glycosylation inhibitor, Celgosivir, (ii) two NS4b-targeting compounds: a 3-Acyl-indole derivative and NITD618, and (iii) two nucleoside viral polymerase inhibitors, 2´CMC and 7DMA...In conclusion, a powerful and robust assay was developed with a fully automated data generation and processing pipeline. It makes the new reporter virus assay amenable to high-throughput screening of large libraries of small molecules."

Journal • Dengue Fever

Drug Repurposing: A Strategy for Discovering Inhibitors against Emerging Viral Infections. (PubMed, Curr Med Chem) - "The conclusions of this review manuscript show the potential of the drug repurposing strategy in the discovery of new pharmaceutical products, as from this approach, drugs that could be used against emerging viral diseases. Thus, this strategy deserves more attention among research groups and is a promising approach to the discovery of new drugs against emerging viral diseases and also other diseases."

Journal • Infectious Disease • Novel Coronavirus Disease

α-glucosidase inhibitors as host-directed antiviral agents with potential for the treatment of COVID-19. (PubMed, Biochem Soc Trans) - "Here, we review and discuss the role of host cell N-glycosylation pathways to virus replication and the drugs available to disrupt these pathways. In particular, we make a case for evaluation of the well-tolerated drugs miglitol, celgosivir and especially miglustat for the treatment of COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease

Iminosugars With Endoplasmic Reticulum α-Glucosidase Inhibitor Activity Inhibit ZIKV Replication and Reverse Cytopathogenicity in vitro. (PubMed, Front Microbiol) - "We investigated the anti-ZIKV ability of three iminosugars with endoplasmic reticulum α-glucosidase inhibitor (ER-AGI) activity, namely deoxynojirimycin (DNJ), castanospermine, and celgosivir...In summary, iminosugars with ER-AGI activity inhibit ZIKV replication and significantly reduce necrosis without altering the antiviral gene expression and apoptosis of infected human cells. The results of this study strongly suggest that iminosugars are promising anti-ZIKV antiviral agents and such warrant further in vivo studies."

Journal • Preclinical

Development of a Cell-Based Immunodetection Assay for Simultaneous Screening of Antiviral Compounds Inhibiting Zika and Dengue Virus Replication. (PubMed, SLAS Discov) - "Sofosbuvir and ribavirin were used to validate the assay, while celgosivir was used to evaluate the ability to discriminate between early and late antiviral activity. In agreement with the proposed mechanism of late action, celgosivir was active against DENV only in the secondary YRA (IC 11.0 ± 1.0 µM) and in PRA (IC 10.1 ± 1.1 µM). The assay format overcomes relevant limitations of the gold standard PRA, allowing concurrent analysis of candidate antiviral compounds against different viruses and providing preliminary information about early versus late antiviral activity."

Journal

Celgosivir or Modipafant as Treatment for Adult Participants With Uncomplicated Dengue Fever in Singapore (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Singapore General Hospital; N=72 ➔ 0; Trial completion date: Sep 2020 ➔ Aug 2019; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Sep 2020 ➔ Aug 2019

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • PCR