galidesivir (BCX4430) / BioCryst - LARVOL DELTA

Exploration of African natural products as VP35 inhibitors to combat Marburg virus infection: Molecular docking, molecular dynamics, and quantum mechanical computations. (PubMed, PLoS One) - "Compared to galidesivir and favipiravir, reference inhibitors, the estimated MM/GBSA binding energies of the identified ANPs with VP35 were about two times lower than galidesivir and favipiravir. These results highlighted the efficacy of computational methods in recognizing putative VP35 inhibitors, providing promising avenues for additional experimental research and prospective curative advancement toward MBV."

Journal • Hematological Disorders • Infectious Disease

Molecular and Structural Insights into Dengue Virus Non-Structural Proteins from Pakistani Clinical Isolates for the Identification of Novel Antiviral Targets. (PubMed, Virus Res) - "In silico modeling and docking studies identified RK-0404678 as a strong binder to NS5 (-6.4 kcal/mol) and Galidesivir to NS5 (-7.2 kcal/mol), suggesting their potential as antiviral candidates. These findings highlight DENV-2 dominance in Pakistan and identify conserved regions in NS5 as promising drug targets, though further experimental validation is warranted."

Journal • Dengue Fever

Conserved Filovirus Proteins as Targets of Broad-Spectrum Antivirals. (PubMed, bioRxiv) - "Conserved filovirus sites targeted for broad-spectrum antivirals.Structural modeling identifies key antiviral binding sites.Viral internal proteins are crucial targets for inhibition.Remdesivir validates conserved polymerase as a druggable target.Study highlights need for pan-filovirus drug screening."

Journal • Ebola Virus Disease • Hematological Disorders • Infectious Disease

Increasing Occurrence of Marburg Virus Outbreaks in Africa: Risk Assessment for Public Health. (PubMed, Microb Biotechnol) - "Compounds included galidesivir, an adenosine nucleoside analogue; favipiravir, a synthetic guanine base analog; remdesivir, an injectable; and obeldesivir, an oral prodrug which are intracellularly metabolised to an adenosine triphosphate nucleotide analog; small interfering RNA drugs that target short segments of the MARV nucleoprotein NP mRNA; and a human neutralising monoclonal antibody directed against MARV glycoprotein. The African CDC has attributed an upper tier risk attribution to MVD when comparing 18 pathogens. For the moment, the short human MARV infection chains make large international outbreaks unlikely, but viral genome analysis in future outbreaks for transmission mutants is warranted."

Journal • Review • Infectious Disease

Multilinear regression analysis of antiviral medications with topological indices. (PubMed, J Mol Graph Model) - "In this research, we investigate degree-based topological indices (TIs) that serve as molecular descriptors for the QSPR analysis of antiviral medications such as Favipiravir, Sertraline, Chloroquine, Ribavirin, Bepridil, Clomifene, Galidesivir, Nilotinib, and Brincidofovir, which affect the interactions between viruses and human proteins. We examine both linear and multilinear QSPR models to analyze the connections between different physical and chemical properties including molecular polarizability (MP), Log P, molecular refractivity (MR), and molecular weight (MW) and the numerical values associated with these drugs. Our results indicate a strong correlation between the topological indices of these antiviral medications and their physical and chemical characteristics."

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Assessing Human Liver Spheroids as a Model for Antiviral Drug Evaluation Against BSL-3 Haemorrhagic Fever viruses. (PubMed, Antiviral Res) - "We successfully demonstrated the antiviral activity of known broad-spectrum antiviral compounds-favipiravir, nitazoxanide, ribavirin, and galidesivir-despite some variability. Overall, we conclude that human liver spheroids cannot replace traditional models for the selection of antiviral compounds but provide valuable additional complementary information. More broadly, this model could be useful to study viral pathogenicity and host-pathogen interactions."

Journal • Hematological Disorders • Respiratory Diseases

Emerging Strategies and Progress in the Medical Management of Marburg Virus Disease. (PubMed, Pathogens) - "Additionally, we have identified several experimental therapies currently under investigation, including antiviral drugs such as favipiravir, galidesivir, obeldesivir, and remdesivir, along with monoclonal and polyclonal antibodies (e.g., polyclonal IgG, monoclonal antibody MR-78-N; MR82-N; MR191-N; monoclonal antibodies MR186-YTE and MBP091). Further investment is needed to accelerate research and optimize these therapeutics and preventive modalities. Additional epidemiological, preclinical, and clinical studies are warranted to generate the evidence required to inform policymaking, resource mobilization, and the implementation of cost-effective interventions for the prevention, control, and treatment of MVD."

Journal • Review • Hematological Disorders • Infectious Disease • IFNB1

Drug repositioning: Identification of potent inhibitors of NS3 protease and NS5 RdRp for control of DENV infection. (PubMed, Biomed Pharmacother) - "Histopathologically, both galidesivir- and tadalafil-treated mice showed alleviation of DENV-induced lesions in the spleen and liver, indicating the potential therapeutic effects of these drugs. These findings highlight the potential of repositioning galidesivir and tadalafil as effective anti-DENV therapies with low cytotoxicity, meeting the urgent global need for new therapeutic agents against this pathogen."

Journal • Dengue Fever • Hepatocellular Cancer • Infectious Disease • Liver Cancer • Solid Tumor

Identification of novel inhibitors of dengue viral NS5 RNA-dependent RNA polymerase through molecular docking, biological activity evaluation and molecular dynamics simulations. (PubMed, J Enzyme Inhib Med Chem) - "The biological activity of the candidates and the reference compounds (BCX4430 and Compound 27) were evaluated on their IC50 values against DENV-NGC, CC50 values, and selectivity index...The comprehensive MD simulations were performed on the candidates to assess the stability behaviour and binding mechanisms. The density functional theory (DFT) analysis was also conducted to explore the structural and electronic properties."

Journal • Dengue Fever

Activity and cryo-EM structure of the polymerase domain of the human norovirus ProPol precursor. (PubMed, J Virol) - "In addition, both galidesivir triphosphate and PPNDS inhibited polymerase activity of GII ProPol, with respective half-maximal inhibitory concentration (IC50) values of 247.5 µM and 3.8 µM...We also show that ProPol responds differently to antivirals than mature polymerase. Altogether, these findings enhance our understanding of the function of the important norovirus ProPol precursor."

Journal • Gastroenterology • Gastrointestinal Disorder • Infectious Disease

Hydroxyl radical-induced C1'-H abstraction reaction of different artificial nucleotides. (PubMed, J Mol Model) - "Recently, a few antiviral drugs viz Molnupiravir (EIDD-1931), Favipiravir, Ribavirin, Sofosbuvir, Galidesivir, and Remdesivir are shown to be beneficial against COVID-19 disease. Subsequently, the structures of these complexes were further optimized by using the ωB97X-D dispersion-corrected density functional theory method and cc-PVTZ basis set in the aqueous medium. The IEFPCM method was used to model the aqueous medium."

Journal • Infectious Disease • Novel Coronavirus Disease

Antiviral therapy for COVID-19 virus: A narrative review and bibliometric analysis. (PubMed, Am J Emerg Med) - "Furthermore, this study examines the published literature about the pharmacological interventions for the novel coronavirus disease 2019 (COVID-19), explicitly focusing on the safety and effectiveness of different medications such as Remdesivir (marketed as Veklury®), Lopinavir/Ritonavir (commercially known as Kaletra® or Aluvia®), Ribavirin, Favipiravir (marketed as Avigan®), Ivermectin, Casirivimab and Imdevimab (branded as Ronapreve®), Sotrovimab (marketed as Xevudy®), Anakinra, Molnupiravir, Nirmatrelvir/Ritonavir (marketed as Paxlovid®), and Galidesivir...Repurposing drugs has been critical in rapidly responding to COVID-19, allowing existing medications to be used in new ways to combat the virus. Combination therapies and further research are essential to optimize treatment strategies."

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

Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. (PubMed, Clin Pathol) - "Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant...Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19."

Journal • Preclinical • Review • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Green and Versatile High Throughput Microwell Oxidation-Based Spectrophotometric Methods for Determination of Galidesivir in Capsules. (PubMed, J AOAC Int) - "Overall, the proposed MW-SPMs are versatile valuable tools for the quantitation of GDV during its pharmaceutical manufacturing."

Journal • Infectious Disease • Novel Coronavirus Disease

Development of Green and High Throughput Microwell Spectrophotometric Methods for Determination of Galidesivir in Bulk Drug and Dosage Forms Based on Simple Oxidimetric Reactions with Inorganic Agents. (PubMed, J AOAC Int) - "Overall, the proposed MW-SPMs are versatile valuable tools for the quantitation of GDV during its pharmaceutical manufacturing."

Journal • Infectious Disease • Novel Coronavirus Disease

Tick-Borne Encephalitis (TBE): From Tick to Pathology. (PubMed, J Clin Med) - "As such, a better understanding of the symptomatology, diagnostics, treatment, and prevention of TBE is required to inform healthcare professionals going forward, which this review addresses in detail. To this end, the need for robust national surveillance data and randomised control trial data regarding the use of various antivirals (e.g., Galidesivir and 7-deaza-2'-CMA), monoclonal antibodies, and glucocorticoids is required to improve the management and outcomes of TBE."

Journal • Review • CNS Disorders • Infectious Disease

Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation. (PubMed, ACS Infect Dis) - "The incorporation of Galidesivir at consecutive sites is strongly disfavored, highlighting the potential for modulation of inhibitory effects of nucleoside analogs by the template sequence. Our results suggest that attenuation of dengue replication by Galidesivir may not derive from the early termination of RNA synthesis following Galidesivir incorporation."

Journal • Dengue Fever • Infectious Disease

Exploring the therapeutic potential of galidesivir analogs against Zaire ebolavirus protein 24 (V24): database screening, molecular docking, drug-relevant property evaluation and molecular dynamics simulations. (PubMed, J Biomol Struct Dyn) - "Both compounds demonstrated high stability within the Z-EBOV-V24 active site over the 150 ns MD simulations. Hence, our study proposes CID 117698807 and CID 117712809 as potential anti-Z-EBOV-V24 drug candidates, warranting further investigation.Communicated by Ramaswamy H. Sarma."

Journal • Ebola Virus Disease • Infectious Disease

Expedient synthesis of imino-C-nucleoside fleximers featuring a one-pot procedure to prepare aryl triazoles. (PubMed, Org Biomol Chem) - "Nucleoside analogues such as the antiviral agents galidesivir and ribavirin are of synthetic interest. This work reports a "one-pot" preparation of similar fleximers using a bifunctional copper catalyst that generates the aryl azide in situ, which is captured by a terminal alkyne to effect triazole formation."

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Differential activity of nucleotide analogs against tick-borne encephalitis and yellow fever viruses in human cell lines. (PubMed, Virology) - "Remdesivir, uprifosbuvir and sofosbuvir were the most potent drugs against TBEV and YFV in liver cells, but they had reduced activity in neural cells, whereas galidesivir retained uniform activity across cell lines and viruses. Ribavirin, valopicitabine, molnupiravir and GS-6620 exhibited only moderate antiviral activity. We found antiviral activity for drugs previously reported as inactive, demonstrating the importance of using human cell lines and comparative experimental assays when screening the activity of nucs. The relatively high antiviral activity of remdesivir, sofosbuvir and uprifosbuvir against TBEV and YFV merits further investigation in clinical studies."

Journal • Preclinical • CNS Disorders

BCX4430 inhibits the replication of rabies virus by suppressing mTOR-dependent autophagy invitro. (PubMed, Virology) - "Meanwhile, BCX4430 showed greater anti-RABV activity than T-705 and anti-RABV activity similar to that of ribavirin in N2a cells. Furthermore, BCX4430 dose- and time-dependently inhibited RABV replication via mTOR-dependent autophagy inhibition in N2a cells with increased phospho-mTOR and phospho-SQSTM1 and decreased LC3-II levels. Taken together, these findings suggest that BCX4430 has potent anti-RABV activity in vitro and might provide a basis for the development of novel drug therapies against RABV."

Journal • Preclinical • Infectious Disease • SQSTM1

An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Bunyavirales Order. (PubMed, ACS Med Chem Lett) - "An iminovir containing the 4-aminopyrrolo[2,1-f][1,2,4-triazine] nucleobase found in remdesivir exhibited submicromolar inhibition of multiple strains of influenza A and B viruses, as well as members of the Bunyavirales order. An efficient synthesis of the 4-aminopyrrolo[2,1-f][1,2,4-triazine]-containing iminovir 2 was developed to enable preliminary in vivo studies, wherein it displayed significant toxicity in BALB/c mice and limited protection against influenza. Further modification of this anti-influenza iminovir will therefore be required to improve its therapeutic value."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Repurposing of potential antiviral drugs against RNA-dependent RNA polymerase of SARS-CoV-2 by computational approach. (PubMed, J Infect Public Health) - "Hence, a comprehensive list of investigational antimicrobial drug compounds such as Favipiravir, Fidaxomicin, Galidesivir, GC376, Ribavirin, Rifabutin, and Umifenovir were computationally evaluated in this study. GC376, Rifabutin, Umifenovir and Remdesivir were identified as the next best compounds. Therefore, the above-mentioned compounds could be considered good leads for further preclinical and clinical experimentations as potentially efficient antiviral inhibitors for combination therapies against SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

In silico structural elucidation of Nipah virus L protein and targeting RNA-dependent RNA polymerase domain by nucleoside analogs. (PubMed, J Biomol Struct Dyn) - "Galidesivir, AT-9010 and Norov-29 scored the top nucleotide analogs to bind to the RdRp...Purine nucleotide analogs are expected to harbor the scaffold for an effective drug against NiV. Finally, this study is expected to provide a start point for medicinal chemistry and drug discovery campaigns toward identification of effective chemotherapeutic agent(s) against NiV.Communicated by Ramaswamy H. Sarma."

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Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies. (PubMed, R Soc Open Sci) - "Based on the galidesivir (BCX4430) chemical structure, 100 compounds were collected and inspected using various in silico approaches...The current data point to the importance of using DL in the drug design process instead of conventional methods such as drug repurposing or database filtration. In conclusion, mol1_069 and mol1_092 are promising anti-EBOV drug candidates that require further in vitro and in vivo investigations."

Journal • Infectious Disease