galidesivir (BCX4430) / BioCryst - LARVOL DELTA

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."

Journal

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."

Journal

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

Quantum chemical studies on the binding domain of SARS-CoV-2 S-protein: human ACE2 interface complex. (PubMed, J Biomol Struct Dyn) - "favipiravir, remdesivir, EIDD, galidesivir, triazavirin, ruxolitinib, and baricitinib...The E of ML complexes better than -40.0 kcal/mol is observed for myricetin, fidarestat, protirelin, m-digallic acid, glucogallin, benserazide hydrochlorideseradie, remdesivir, tazobactum, sapropterin, nitrofurantoin, quinonoid, pyruvic acid calcium isoniazid, and aspartame, and among them the highest E -85.4 kcal/mol is observed for myricetin...The ONIOM-level study is found to be effective for the interpretation of the noncovalent interactions resulting from residues such as arginine, histidine, tyrosine, lysine, carboxylate, and amide moieties in the active site and suggests rational design strategies for COVID-19 drug development. Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

In-silico study for the screening and preparation of ionic liquid-AVDs conjugate to combat COVID-19 surge. (PubMed, J Mol Liq) - "In the present study strategically, we performed the blind molecular docking of antiviral drug (Abacavir, Acyclovir, and Galidesivir)-choline based ILs conjugates with the target protein (M protease). Additionally, the energetic profiling of the ILs drugs and their conjugates was done using DFT calculations which revealed the stability of the conjugates and have a better option to be developed as a therapeutic agent. Also, from molecular dynamic simulation was done and results showed the stability of the complex formed between target protein and the designed conjugates of AVDs and ILs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective. (PubMed, Future Microbiol) - "The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before. Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp. The present in silico study suggests the dual inhibition potential of the recommended drugs and compounds against SARS-CoV-2 and R. oryzae RdRps."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

INSIGHTS INTO THE BIOLOGICAL IMPACT OF COVID-19 AND ITS VACCINES ON HUMAN HEALTH. (PubMed, Saudi J Biol Sci) - "The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use...Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body..."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics and Safety of the Nucleoside Analog Antiviral Drug Galidesivir Administered to Healthy Adult Subjects. (PubMed, Clin Pharmacol Drug Dev) - "No clinically significant dose-related trends in laboratory values, vital signs, electrocardiograms, or echocardiograms were noted. Galidesivir was safe and generally well tolerated."

Journal • PK/PD data • Infectious Disease • Respiratory Diseases

Synthesis of galidesivir from L-mannose (ACS-Sp 2022) - "The proposed synthesis starting from commercially-available L-mannose is 15 steps and is projected to give a better overall yield. Thus far, the hydroxyl groups of the L-mannose were appropriately derivatized and the sugar ring was opened by reductive elimination to render an aldehyde that cyclizes to form a five-membered hemiacetal ring 7."

Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Oncology • Respiratory Diseases