Journal: bioRxiv

Article Title: Predicting clinical outcomes of SARS-CoV-2 drug treatments with a high throughput human airway on chip platform

doi: 10.1101/2022.06.07.495101

Figure Lengend Snippet: Comparison between the antiviral effects of 5 drug compounds against SARS-CoV-2 infection in primary human epithelial tissue from donor 04401 grown in a PREDICT96-ALI plate: (A) Nirmatrelvir, (B) Molnupiravir, (C) Remdesivir, (D) PF-00835231, and (E) Calpeptin. Antiviral drugs were diluted in Pneumacult ALI medium, added 2 h after infection, and again on days 2 and 4 at the concentrations indicated. Apical sides of tissues were washed with HBSS to collect viral supernatant from which SARS-CoV-2 viral genomes were quantified by RT-qPCR, probing for the N1 gene target. N=4 tissue devices per condition (except untreated samples, n=8). Data collected from the same experiment displayed in and representative of 2 independent experiments. Statistical significance determined by a two-way analysis of variance (ANOVA) with Dunnett’s test for multiple comparisons (comparing to infected/untreated): P > 0.05; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001. Unlabeled lines indicate no significant different from infected/untreated (gray) line.

Article Snippet: Nirmatrelvir (MedChemExpress), PF-00835231 (MedChemExpress), Molnupiravir (Tocris Bioscience), Calpeptin (Tocris Bioscience) and Remdesivir (Tocris Bioscience) were used in anti- viral screens performed on PREDICT96-ALI tissue.

Techniques: Comparison, Infection, Quantitative RT-PCR

Journal: bioRxiv

Article Title: Predicting clinical outcomes of SARS-CoV-2 drug treatments with a high throughput human airway on chip platform

doi: 10.1101/2022.06.07.495101

Figure Lengend Snippet: Image quantification of SARS-CoV-2 infected tissues nucleocapsid positive (+) cells shows tissue response to 5 drug compounds 6 days post inoculation of SARS-CoV-2 infection in primary human epithelial tissue from donor 04401 grown in a PREDICT96-ALI plate: (A) Nirmatrelvir, (B) Molnupiravir, (C) Remdesivir, (D) PF-00835231, and (E) Calpeptin. Briefly, tissues were stained for nuclei (DAPI) and SARS-CoV-2 nucleocapsid (N) protein. Using the Celigo software, the percentage of nuclei corresponding to cells positive for the nucleocapsid protein was quantified. (F) Controls: Untreated, uninfected (solid gray bar), untreated, infected (patterned bar), and vehicle treated, infected (black bar). (G) Representative monochromatic fluorescence images of uninfected and SARS-CoV-2-infected tissues stained for SARS-CoV-2 nucleocapsid. All data in this figure collected from the same experiment displayed in and representative of 2 independent experiments. Bar graphs show mean ± standard deviation; n=4 tissue devices per condition (except untreated samples, n=8). Statistical significance determined by a one-way analysis of variance (ANOVA) with Dunnett’s test for multiple comparisons (comparing to infected/untreated): no significance (ns), P > 0.05; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001. Unlabeled bars indicate no significance.

Article Snippet: Nirmatrelvir (MedChemExpress), PF-00835231 (MedChemExpress), Molnupiravir (Tocris Bioscience), Calpeptin (Tocris Bioscience) and Remdesivir (Tocris Bioscience) were used in anti- viral screens performed on PREDICT96-ALI tissue.

Techniques: Infection, Staining, Software, Fluorescence, Standard Deviation

Journal: medRxiv

Article Title: Pharmacokinetics of ß-d-N4-hydroxycytidine, the active metabolite of prodrug molnupiravir, in non-plasma compartments of patients with SARS-CoV-2 infection

doi: 10.1101/2021.12.06.21267342

Figure Lengend Snippet: Geometric mean NHC concentrations over time from saliva (closed points, solid line), nasal swabs (open points, solid line) and tear strips (closed points, broken line) of individuals with SARS-CoV-2 following ( A ) single dose (Day 1) and ( B ) multiple dose (Day 5) molnupiravir 300 mg (circles), 600 mg (squares) and 800 mg (diamonds) twice daily. Data are expressed on a log-linear scale.

Article Snippet: Of note, NHC exists predominantly in unbound form in plasma (unbound fraction ≥0.99) ( personal communication, Ridgeback Biotherapeutics ) and in vitro studies demonstrated that molnupiravir and NHC are not substrates for efflux transporters ABCB1 (p-glycoprotein), ABCC2 (multidrug resistance-associated protein 2; MRP2) or ABCG2 (breast cancer resistance protein, BCRP; personal communication, Ridgeback Biotherapeutics ), suggesting salivary excretion of NHC is potentially modulated by other factors relating to the characteristics of the drug or surrounding milieu.

Techniques:

Journal: medRxiv

Article Title: Pharmacokinetics of ß-d-N4-hydroxycytidine, the active metabolite of prodrug molnupiravir, in non-plasma compartments of patients with SARS-CoV-2 infection

doi: 10.1101/2021.12.06.21267342

Figure Lengend Snippet: Matched NHC concentrations from ( A ) saliva, ( B ) nasal swabs and ( C ) tear strips versus plasma concentrations following single dose (Day 1; left pane) and multiple dose (Day 5; right pane) molnupiravir 300 mg, 600 mg and 800 mg twice daily. Concentrations at each dose were pooled, log10 transformed and analysed using linear regression; p ≤ 0.05 was considered statistically significant.

Article Snippet: Of note, NHC exists predominantly in unbound form in plasma (unbound fraction ≥0.99) ( personal communication, Ridgeback Biotherapeutics ) and in vitro studies demonstrated that molnupiravir and NHC are not substrates for efflux transporters ABCB1 (p-glycoprotein), ABCC2 (multidrug resistance-associated protein 2; MRP2) or ABCG2 (breast cancer resistance protein, BCRP; personal communication, Ridgeback Biotherapeutics ), suggesting salivary excretion of NHC is potentially modulated by other factors relating to the characteristics of the drug or surrounding milieu.

Techniques: Clinical Proteomics, Transformation Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

doi: 10.1038/s41392-023-01724-w

Figure Lengend Snippet: The summary of authorized or approved COVID-19 therapeutics

Article Snippet: , Molnupiravir (Lagevrio) , Merck , Inhibition of RdRp replication , Oral; 800 mg twice daily for 5 days. , Mild to moderate COVID-19 adult patients a , Approval on 4 November 2021 in the UK; Authorized EUA in many other countries. , – .

Techniques: Inhibition, Injection, Mutagenesis, Virus

Journal: Signal Transduction and Targeted Therapy

Article Title: Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

doi: 10.1038/s41392-023-01724-w

Figure Lengend Snippet: SARS-CoV-2 life cycle and the potential mechanisms of anti-SARS-CoV-2 therapeutics. (1) Binding to cell: the SARS-CoV-2 Spike protein recognizes and binds to the ACE2 receptor on host cells, initiating the process of cellular attachment. This step can be inhibited by neutralizing antibodies from convalescent plasma and monoclonal antibodies; (2) Fusion or endocytosis: subsequent to attachment, viral fusion or endocytosis with the host cell membrane ensues. Azithromycin, Hydroxychloroquine, and Chloroquine possess the capacity to modulate this crucial process; (3) Uncoating and genome release: viral uncoating follows, leading to the release of the viral genome and initiation of primary translation. M-pro inhibitors, like Lopinavir and Paxlovid, are tailored to impede this specific stage; (4) RdRp complex assembly: drugs such as Remdesivir, Molnupiravir, and Ribavirin specifically target the assembly process; (5) Viral RNA transcription and replication; (6) Translation of viral mRNA: viral mRNA translates into Nucleocapsid (N) and structural proteins (S, M, and E proteins); (7) Translocated into ER and Golgi: structural proteins are subsequently translocated into the ER and Golgi for maturation. Hydroxychloroquine and Chloroquine can block this process. (8) Formation of Virions: structural proteins combine with the nucleocapsid; (9) Virus release. Notably, interferons exert regulatory effects at multiple stages of the viral life cycle

Article Snippet: , Molnupiravir (Lagevrio) , Merck , Inhibition of RdRp replication , Oral; 800 mg twice daily for 5 days. , Mild to moderate COVID-19 adult patients a , Approval on 4 November 2021 in the UK; Authorized EUA in many other countries. , – .

Techniques: Binding Assay, Cell Attachment Assay, Membrane, Blocking Assay, Virus

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet: Results from molnupiravir MOVe-OUT trial in adults with mild-to-moderate COVID-19 [ [14] , [21] , [22] , [23] , [24] ].

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques:

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet: Subgroups who appeared to have no benefit in hospitalization or death through day 29 with molnupiravir over placebo [ [14] , [21] , [22] , [23] , [24] ].

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques:

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet: Comparative efficacy data of EUA/authorized # drugs for COVID-19 [ [14] , [28] , [29] , [30] , [31] , [32] ].

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques: In Vitro

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet:

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques: Infection

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet:

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques: Bioprocessing

Journal: Diabetes & Metabolic Syndrome

Article Title: An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 ☆

doi: 10.1016/j.dsx.2022.102396

Figure Lengend Snippet:

Article Snippet: For example-primary outcome was all-cause hospitalization or death for molnupiravir (MOVe-OUT), nirmatrelvir-ritonavir (EPIC-HR) and sotrovimab (COMET-ICE) while it was COVID-19-related hospitalization or death for casirivimab–imdevimab (REGEN-COV), bamlanivimab–etesevimab (BLAZE-1) and remdesivir (PINETREE).

Techniques: Infection