molnupiravir  (MedChemExpress)

Journal: bioRxiv

Article Title: Discovery of host-directed modulators of virus infection by probing the SARS-CoV-2-host protein-protein interaction network

doi: 10.1101/2022.06.03.494640

Figure Lengend Snippet: Dose-response matrix of SARS-CoV-2-infected 293TAT cells when combining molnupiravir (MPV, EIDD-1931) with either (A) MPA or (B) merimepodib. The maximum synergistic area (MSA, dotted-line square) and the Bliss synergy score were calculated with SynergyFinder v2.0, both for efficacy (virus infection) and viability (toxic effect on non-infected cells). Selective efficacy quantifies the difference in inhibition of virus-infected and mock-infected cells. A selective efficacy of 100 means that the drug combination inhibits 100% of the virus-infected cells and does not affect the mock-infected, drug-treated cells, while a selective efficacy of 0 means the drug kills both the virus and mock-infected cells. The selective efficacies of 46% and 35% for combinations of molnupiravir with MPA and merimepodib, respectively, indicate relatively high selective suppression of virus infection only. This is also seen in minimal co-inhibition of the viability of non-infected cells (right).

Article Snippet: Compounds vorinostat (catalogue number S1047; Sellckchem), romidespin (catalogue number S3020; Sellckchem), spautin-1 (catalogue number S7888; Sellckchem), fedratinib (catalogue number S2736; Sellckchem), merimepodib (catalogue number S6689; Sellckchem), mycophenolic acid (catalogue number HYB0421; MedChem Express), (+)-JQ-1 (catalogue number HY13030; MedChem Express) and Molnupiravir (catalogue number HY125033 MedChem Express) were tested.

Techniques: Infection, Inhibition

Journal: Toxicology and Applied Pharmacology

Article Title: Molnupiravir; molecular and functional descriptors of mitochondrial safety

doi: 10.1016/j.taap.2022.116003

Figure Lengend Snippet: Concentration-dependent Effect of Molnupiravir and NHC on Mitochondrial and Nuclear Gene Expression. Panels A and C-H) HepG2 cells were exposed in culture to increasing concentrations of Molnupiravir or NHC for 48 hours. RNA was extracted and RT-qPCR performed to quantify gene transcripts. Values represent mRNA copies normalized to 18s ribosomal RNA. B) HepG2 cells were exposed to a sub-cytotoxic concentration of 2’-C-methyladeonsoine (25 μM 2-C-MA) as a positive control for mitochondrial RNA polymerase inhibition. The plots represent the mean +/− S.D. for 4 independent replications and asterisks indicate a statistically significant difference compared to the respective 0 μM dose group (Dunnett's P

Article Snippet: 2.2 Chemical exposure Molnupiravir (EIDD-2801, MK-4482; Mol) was purchased from MedChemExpress (Item no. HY-135853). β-D-N4 -hydroxycytidine (EIDD-1931; NHC) was purchased from Cayman Chemicals (item no. 9002958).

Techniques: Concentration Assay, Expressing, Quantitative RT-PCR, Positive Control, Inhibition

Journal: Toxicology and Applied Pharmacology

Article Title: Molnupiravir; molecular and functional descriptors of mitochondrial safety

doi: 10.1016/j.taap.2022.116003

Figure Lengend Snippet: Concentration-dependent Effect of Molnupiravir and NHC on Mitochondrial DNA Copy Number – A) HepG2 cells were exposed to increasing concentrations of either Molnupiravir or NHC for 48 hours. At the end of the exposure, DNA was extracted and quantified by qPCR using the recommended nuclear (nDNA) and mitochondrial (mtDNA) gene targets ( Malik et al., 2011 ). B) HepG2 cells were exposed to sub-cytotoxic concentration of 2′, 3′ –dideoxycytidine (40 nM ddC) for 48 hours as a positive control for mtDNA depletion. For both panels, values represent the ratio of mtDNA/nDNA gene dose and are expressed as the mean +/− S.D. for 4 independent determinations. Asterisks indicate the statistically significant difference compared to zero drug concentration (Student's t-test P

Article Snippet: 2.2 Chemical exposure Molnupiravir (EIDD-2801, MK-4482; Mol) was purchased from MedChemExpress (Item no. HY-135853). β-D-N4 -hydroxycytidine (EIDD-1931; NHC) was purchased from Cayman Chemicals (item no. 9002958).

Techniques: Concentration Assay, Real-time Polymerase Chain Reaction, Positive Control

Journal: Toxicology and Applied Pharmacology

Article Title: Molnupiravir; molecular and functional descriptors of mitochondrial safety

doi: 10.1016/j.taap.2022.116003

Figure Lengend Snippet: Mitochondrial Respiration Parameters Associated with Molnupiravir or NHC Cell Exposure. Oxygen consumption rates (OCR), normalized to protein concentration as determined by the SRB assay, were measured for HepG2 cells exposed to increasing concentrations of Molnupiravir (Mol) or NHC for 48 h. Panel A illustrates the sequence of additions for the Seahorse XF Extracellular Flux Analyzer Mito Stress Test and the areas reflecting the corresponding respiratory parameters as defined in panels B, C and D. Each panel represents a parameter calculated according to the Seahorse XF Cell Mito Stress Test Report Generator (Agilent) and each bar reflects the mean +/− S.D. for 4 independent experimental observations. Asterisks (*) indicate a statistically significant difference compared to the zero drug control (Dunnett's, P ≤ 0.05).

Article Snippet: 2.2 Chemical exposure Molnupiravir (EIDD-2801, MK-4482; Mol) was purchased from MedChemExpress (Item no. HY-135853). β-D-N4 -hydroxycytidine (EIDD-1931; NHC) was purchased from Cayman Chemicals (item no. 9002958).

Techniques: Protein Concentration, Sulforhodamine B Assay, Sequencing

Journal: Toxicology and Applied Pharmacology

Article Title: Molnupiravir; molecular and functional descriptors of mitochondrial safety

doi: 10.1016/j.taap.2022.116003

Figure Lengend Snippet: Concentration-dependent Cytotoxicity of Molnupiravir and NHC – HepG2/C3A cells were exposed to increasing concentrations of either Molnupiravir or NHC for 48 hours in 24-well plates. At the end of the exposure the cells were fixed with methanol and stained with sulphorhodamine B (SRB). The bound SRB was solubilized in 10 mM Tris base and the absorbance measured 540nm. Values represent the mean +/− SD for 4 independent determinations. Asterisks (*) represent a statistically significant difference (P

Article Snippet: 2.2 Chemical exposure Molnupiravir (EIDD-2801, MK-4482; Mol) was purchased from MedChemExpress (Item no. HY-135853). β-D-N4 -hydroxycytidine (EIDD-1931; NHC) was purchased from Cayman Chemicals (item no. 9002958).

Techniques: Concentration Assay, Staining, Sulforhodamine B Assay

Journal: bioRxiv

Article Title: Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

doi: 10.1101/2022.06.27.497875

Figure Lengend Snippet: Histopathology and immunohistochemistry analysis of SARS-CoV-2-infected mice treated with 20 mg/kg body weight nirmatrelvir, remdesivir, and molnupiravir monotherapy and their combinations, nirmatrelvir-remdesivir, and nirmatrelvir-molnupiravir. (A) Pathological changes and virus distribution were measured at 5 DPI in the lung tissue by H E staining and immunohistochemical staining with an anti-nucleocapsid antibody, respectively. Images are shown at both low (5X) and high (20X) power resolution. (B) Neuronal death and virus distribution were measured at 5 DPI in brain tissue by H E staining and immunohistochemistry, respectively. Images are shown at low (10X) and high (20X) power resolutions.

Article Snippet: Compound sourcesNirmatrelvir and molnupiravir were purchased from MedChemExpress (Monmouth Junction, USA).

Techniques: Histopathology, Immunohistochemistry, Infection, Mouse Assay, Staining

Journal: bioRxiv

Article Title: Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

doi: 10.1101/2022.06.27.497875

Figure Lengend Snippet: Evaluation of the therapeutic efficacy of nirmatrelvir, remdesivir, and molnupiravir monotherapies and their combinations, nirmatrelvir-remdesivir, and nirmatrelvir-molnupiravir, in SARS-CoV-2-infected K18-hACE2 transgenic mice. (A) Schematic illustration of the study design. Mice were infected with 5 MLD50 of SARS-CoV-2 followed by administration of 20 mg/kg drugs for 5 consecutive days. Disease progression and other clinical parameters were monitored until 14 DPI, and the brain and lung were collected at 5 DPI for viral titer estimation and histopathological and immunohistochemical analyses. (B) Body weight was monitored daily for 14 days and is expressed as a percentage relative to the initial body weight on day 0. (C) Kaplan–Meier plot of the survival of all the groups (log-rank Mantel-Cox; **p

Article Snippet: Compound sourcesNirmatrelvir and molnupiravir were purchased from MedChemExpress (Monmouth Junction, USA).

Techniques: Infection, Transgenic Assay, Mouse Assay, Immunohistochemistry

Journal: bioRxiv

Article Title: Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

doi: 10.1101/2022.06.27.497875

Figure Lengend Snippet: Evaluation of the viral load in SARS-CoV-2-infected mice treated with nirmatrelvir, remdesivir, and molnupiravir monotherapies, their combinations, nirmatrelvir-remdesivir, and nirmatrelvir-molnupiravir. (A) Lungs and brains were collected at 5 DPI, and viral titers were estimated. The viral titer is expressed in log10 PFU/mL, and the limit of detection is shown in a dotted line (one-way ANOVA with Tukey’s multiple comparison test; *p

Article Snippet: Compound sourcesNirmatrelvir and molnupiravir were purchased from MedChemExpress (Monmouth Junction, USA).

Techniques: Infection, Mouse Assay

Journal: bioRxiv

Article Title: Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.

doi: 10.1101/2021.09.13.460111

Figure Lengend Snippet: Evaluation of therapeutic intervention of GS-621763 in comparison to molnupiravir (MPV). (A) Depicted is the % starting weight in therapeutically treated mice with either 30 mg/kg or 60 mg/kg GS-621763 or MPV at 12 or 24 hrs (n=10 for all treatment groups). All mice were infected with 1×10 4 PFU SARS-CoV-2 MA10. (B) Lung viral titers in therapeutically treated mice with either 30 mg/kg or 60 mg/kg GS-621763 or MPV at 12 or 24 hrs (n=10 for all treatment groups). All mice were infected with 1×10 4 PFU SARS-CoV-2 MA10. Limit of detection (LoD). (C) Viral N RNA in therapeutically treated mice with either 30 mg/kg or 60 mg/kg GS-621763 or MPV at 12 or 24 hrs (n=10 for all treatment groups). All mice were infected with 1×10 4 PFU SARS-CoV-2 MA10. (D) Pulmonary function in therapeutically treated mice with either 30 mg/kg or 60mg/kg GS-621763 or MPV at 12 or 24 hrs (n=4 for all treatment groups). All mice were infected with 1×10 4 PFU SARS-CoV-2 MA10. (F and G) Lung pathology in the therapeutically treated mice with either 30 mg/kg or 60 mg/kg GS-621763 or MPV at 12or 24 hrs (n=10 for all treatment groups). All mice were infected with 1×10 4 PFU SARS-CoV-2 MA10. Data were analyzed using two-way ANOVA (weight loss and lung function) and Kruskal-Wallis test (lung titer, lung viral RNA, and pathology scores), *p

Article Snippet: Molnupiravir was purchased from MedChemExpress LLC (NJ, USA) with a purity of 95% based on HPLC analysis.

Techniques: Mouse Assay, Infection