Journal: Journal of Virology

Article Title: Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

doi: 10.1128/jvi.00740-25

Figure Lengend Snippet: NHC inhibits BRBV infection in cell culture. ( A through D ) A549 cells inoculated with BRBV (MOI of 0.01) in the presence or absence of different concentrations of ( A ) NHC, ( B ) galidesivir, ( C ) remdesivir, and ( D ) sofosbuvir. The virus titer in the culture supernatant was quantified in 12, 24, 48, and 72 h. Values are means (± standard error of the mean) of the virus titer from three experiments performed in duplicate. ** P < 0.01, *** P < 0.005 by one-way ANOVA on the area under the curves fit by linear regression of log-transformed virus titer over time and compared with Dunnett’s multiple comparisons. The dotted line represents the limit of detection at 200 FFU/mL. ( E ) Inhibition comparison of NHC and favipiravir in A549 cells at 48 hpi, including the indicated 50% effective concentration (EC 50 ). A curve was fitted through the data using the log(inhibitor) vs. response-variable slope equation (GraphPad Prism 10.0).

Article Snippet: Next, the cells were treated with different concentrations of remdesivir (Selleckchem; S8932), sofosbuvir (Selleckchem; S2794), N 4 -hydroxycytidine (NHC; Selleckchem; S0833), favipiravir (Selleckchem; S7975), or galidesivir (MedChemExpress; HY-18649/CS-3778) for 2 h in serum-free DMEM.

Techniques: Infection, Cell Culture, Virus, Transformation Assay, Inhibition, Comparison, Concentration Assay

Journal: Frontiers in Microbiology

Article Title: Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges

doi: 10.3389/fmicb.2023.1239079

Figure Lengend Snippet: Ongoing clinical trials for therapeutics.

Article Snippet: 4. , An investigation on the safety, tolerability, and pharmacokinetics of a single dose of IV BCX4430 , US-Kansas City, Lenexa, PRA Health Sciences , Marburg Virus , Drug: Galidesivir , Active, not recruiting , .

Techniques: Clinical Proteomics, Virus, Vaccines, Drug discovery

Journal: Journal of Infection and Public Health

Article Title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

doi: 10.1016/j.jiph.2016.04.002

Figure Lengend Snippet: Anabolism of BCX4430 to BCX4430-TP (BCX6870) in hepatocytes in vitro (left panel) and levels of BCX4430 in the plasma and BCX4430-TP in the liver of rats after an IM injection of BCX4430 (right panel). Redrawn from . Cells were incubated with 10 μM BCX4430 for the indicated times, and the levels of BCX4430-TP were quantitated by HPLC; the plasma samples were obtained and the livers were harvested from rats following administration of a 30 mg/kg BCX4430 dose by intramuscular injection, and the plasma BCX4430 and the liver BCX4430-TP were quantitated by HPLC/tandem MS.

Article Snippet: To date, BCX4430 has shown efficacy in a lethal rodent and an NHP model of filoviral diseases (Marburg virus disease [MVD] and Ebola virus disease [EVD]) , as well as in rodent models of Yellow Fever and Rift Valley fever .

Techniques: In Vitro, Clinical Proteomics, Injection, Incubation

Journal: Journal of Infection and Public Health

Article Title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

doi: 10.1016/j.jiph.2016.04.002

Figure Lengend Snippet: Structure of BCX4430 (left panel), an adenosine nucleoside analog broad-spectrum antiviral drug, and its active nucleotide form, BCX4430-triphosphate (also designated as BCX6870) (right panel).

Article Snippet: To date, BCX4430 has shown efficacy in a lethal rodent and an NHP model of filoviral diseases (Marburg virus disease [MVD] and Ebola virus disease [EVD]) , as well as in rodent models of Yellow Fever and Rift Valley fever .

Techniques:

Journal: Journal of Infection and Public Health

Article Title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

doi: 10.1016/j.jiph.2016.04.002

Figure Lengend Snippet: Non-obligate chain termination of hepatitis C through RNA-dependent, template-directed RNA synthesis by incubation with BCX4430 triphosphate (BCX6870) in vitro. Chain termination as a result of incorporation of BCX4430 is shown in lanes 5 and 8. Lanes 4 and 7 show 3′-deoxyATP, a known obligate chain terminator positive control. Lane 6 shows the pattern of RNA oligomers made with no inhibitors present or normal nucleotides present.

Article Snippet: To date, BCX4430 has shown efficacy in a lethal rodent and an NHP model of filoviral diseases (Marburg virus disease [MVD] and Ebola virus disease [EVD]) , as well as in rodent models of Yellow Fever and Rift Valley fever .

Techniques: Incubation, In Vitro, Positive Control

Journal: Journal of Infection and Public Health

Article Title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

doi: 10.1016/j.jiph.2016.04.002

Figure Lengend Snippet: Variation in and low efficiency of conversion of BCX4430 to BCX4430-TP in cell lines commonly used for in vitro evaluation of antiviral activity of test agents; the data shown indicate mean and SD. Redrawn from ; right-hand scale indicates the percent of BCX4430-TP mean levels observed at 24 h in fresh human hepatocytes. The cell lines were incubated with 10 μM BCX4430 for the indicated times, and the levels of BCX4430-TP were quantitated by HPLC.

Article Snippet: To date, BCX4430 has shown efficacy in a lethal rodent and an NHP model of filoviral diseases (Marburg virus disease [MVD] and Ebola virus disease [EVD]) , as well as in rodent models of Yellow Fever and Rift Valley fever .

Techniques: In Vitro, Activity Assay, Incubation

Journal: Journal of Infection and Public Health

Article Title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

doi: 10.1016/j.jiph.2016.04.002

Figure Lengend Snippet: Relationship between the dose of BCX4430 to the antiviral effect (left panel) and survival (right panel) in Syrian golden hamsters inoculated with the Yellow Fever virus. The left panel open symbols shows data for each animal ( n = 10 per dose group), and the horizontal bars shows the geometric mean for each dose group; the inset shows the best-fit nonlinear regression of BCX4430 dose with viral load (GraphPad Prism v6.07), indicating a typical and steep concentration–inhibition relationship. The right panel closed symbols show the proportion of animals surviving at each dose level in the same experiment, with error bars indicating the exact binomial confidence intervals. The line shows the best-fit logistic regression of dose with proportion surviving (XLSTAT Version 2015.5.01.23039).

Article Snippet: To date, BCX4430 has shown efficacy in a lethal rodent and an NHP model of filoviral diseases (Marburg virus disease [MVD] and Ebola virus disease [EVD]) , as well as in rodent models of Yellow Fever and Rift Valley fever .

Techniques: Virus, Concentration Assay, Inhibition

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Three-dimensional representation of binding modes for the best two inhibitors and the reference molecule BCX4430.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: Binding Assay

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Calculated molecular docking scores (in kcal mol −1 ) and binding features for BCX4430, mol1_069 and mol1_092.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: Binding Assay

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Nine poses of molecular docking for the best two compounds and BCX4430.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques:

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: The calculated MM/GBSA binding energies for mol1_069, mol1_092 and the reference molecule BCX4430.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: Binding Assay

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Evaluated binding energies per frame for BCX4430, mol1_069 and mol1_092 towards EBOVVP24 over 100 ns MD simulations.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: Binding Assay

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: MM/GBSA binding energy and docking scores of BCX4430, the highest two compounds (mol1_069 and mol1_092) and the lowest two compounds (mol1_028 and mol1_013).

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: Binding Assay

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Drug-likeness for the highest ranked compounds and the standard molecule BCX4430.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques:

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Physico-chemical properties for the best two compounds and BCX4430.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques:

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Medicinal chemistry of the reference molecule BCX4430, mol1_069 and mol1_092.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques:

Journal: Royal Society Open Science

Article Title: Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

doi: 10.1098/rsos.220369

Figure Lengend Snippet: Predicted toxicities for BCX4430, mol1_069 and mol1_092.

Article Snippet: On the other hand, BCX4430 scored one violation each for Lipinski (NHorOH > 5), Ghose (WLOGP < −0.4), Veber (TPSA > 140) and Egan (TPSA > 131.6), and two violations for Muegge (XLOGP3<−2, H-don > 5).

Techniques: