WO2021214296A1 - Traitement d'infections par un coronavirus - Google Patents

Traitement d'infections par un coronavirus Download PDF

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Publication number
WO2021214296A1
WO2021214296A1 PCT/EP2021/060672 EP2021060672W WO2021214296A1 WO 2021214296 A1 WO2021214296 A1 WO 2021214296A1 EP 2021060672 W EP2021060672 W EP 2021060672W WO 2021214296 A1 WO2021214296 A1 WO 2021214296A1
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gfr
antagonist
subject
inhibitor
virus
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PCT/EP2021/060672
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English (en)
Inventor
Christian MÜNCH
Jindrich Cinatl
Kevin KLANN
Denisa BOJKOVA
Sandra Ciesek
Georg Claudius TASCHER
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Johann Wolfgang Goethe-Universität Frankfurt am Main
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Publication of WO2021214296A1 publication Critical patent/WO2021214296A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Definitions

  • Severe acute respiratory syndrome coronavirus 2 (SARS-C0V-2), a novel coronavirus, has been rapidly spreading around the globe since the beginning of 2020. In people, it causes coronavirus disease 2019 (COVID-19) often accompanied by severe respiratory syndrome (Chen et ah, 2020; Zhao et ah, 2020; Zhu et ah, 2020). To conquer the global health crisis triggered by COVID-19, rapidly establishing drugs is required to dampen the disease course and relieve healthcare institutions. However, the development of novel drugs specifically targeting a virus usually takes several years, including clinical trials. Thus, repurposing of already available and (ideally) approved drugs might be essential to rapidly treat COVID-19.
  • EGFR epidermal growth factor receptor
  • Epstein-Barr virus influenza or hepatitis C
  • Eierhoff et ah, 2010; Rung et ah, 2011; Lupberger et ah, 2011 Since GFR regulates various proliferative pathways, activation of GFR signalling might prove beneficial for virus replication and maintenance. Indeed, it was shown that EGFR signalling can suppress interferon signalling and thus the antiviral response elicited in respiratory virus diseases, such as influenza A and rhinovirus (Ueki et ah, 2013). Activation of GFR signalling might play an important role also in other respiratory viruses, such as SARS-C0V-2.
  • growth factor receptor refers to proteins that bind specific signalling molecules. The receptors frequently interact with kinases and other proteins involved in signal transduction pathways. Growth factor receptors include, but are not limited to epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), insulin-like growth factor receptor (IGFR), platelet derived growth factor (PDGF), transforming growth factor (TGF), and nerve growth factor receptor.
  • EGFR epidermal growth factor receptor
  • VEGFR vascular endothelial growth factor receptor
  • FGFR fibroblast growth factor receptor
  • IGFR insulin-like growth factor receptor
  • PDGF platelet derived growth factor
  • TGF transforming growth factor
  • subject is used interchangeably herein to refer to a mammal, including, but not limited to, murines (rats, mice), felines, non-human primates (e.g., simians), humans, canines, ungulates, etc.
  • a “subject” is a human, and can also be referred to as a “patient.”
  • Administration of an effective amount of a GFR antagonist to an individual having a virus infection results in one or more of: 1) a reduction in viral load; 2) a reduction in viral load in a target biological sample; 3) a reduction in the spread of a virus from one epithelial cell to another cell in an individual; 4) a reduction in viral entry into (e.g., reduction of internalization of a virus into) an epithelial cell; 5) a reduction in time to seroconversion (virus undetectable in patient serum); 6) an increase in the rate of sustained viral response to therapy; 7) a reduction of morbidity or mortality in clinical outcomes; and 8) an improvement in an indicator of disease response (e.g., a reduction in one or more symptoms of a viral infection, such as fever, etc.).
  • an indicator of disease response e.g., a reduction in one or more symptoms of a viral infection, such as fever, etc.
  • an “effective amount” of a GFR antagonist is an amount that, when administered in one or more doses to an individual having a virus infection, is effective to reduce the number of genome copies of the virus in the individual by at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the number of genome copies in the individual in the absence of treatment with the antagonist.
  • a method of treating a virus infection where the virus is HC0V-229E, the method involving administering an effective amount of a GFR antagonist to an individual infected with HC0V-229E.
  • a method of treating a virus infection is provided, where the virus is SARS-CoV, the method involving administering an effective amount of an GFR antagonist to an individual infected with SARS-CoV.
  • the individual is a human of from about one month to about 6 months, from about 6 months to about 1 year, from about 1 year to about 5 years, from about 5 years to about 12 years, from about 13 years to about 18 years, from about 18 years to about 25 years, from about 25 years to about 50 years, from about 50 years to about 75 years of age, or older than 75 years of age.
  • the individual has a chronic lung disease (e.g., emphysema, chronic bronchitis, asthma, cystic fibrosis, bronchiectasis, COPD, or interstitial lung disease).
  • the individual has, in addition to a coronavirus infection, pneumonia, where the pneumonia is caused by the coronavirus (preferably SARS-C0V-2) or by a bacterial infection.
  • the human subject is immunecompromised.
  • MEK or RAF inhibitor refers to a molecule that decreases, blocks, inhibits, abrogates, or interferes with signal transduction through the MAPK pathway (e.g., the RAF/MEK/ERK MAPK pathway).
  • a MEK or RAF inhibitor may inhibit the activity of one or more proteins involved in the activation of MEK or RAF signalling.
  • a MEK or RAF signalling inhibitor may activate the activity of one or more proteins involved in the inhibition of MEK or RAF signalling.
  • a respiratory virus causes exacerbation of a chronic lung disease (e.g., asthma, COPD, cystic fibrosis, emphysema, chronic bronchitis, interstitial lung disease, bronchitis; sarcoidosis, idiopathic pulmonary fibrosis, bronchiectasis, bronchiolitis, etc.).
  • a chronic lung disease e.g., asthma, COPD, cystic fibrosis, emphysema, chronic bronchitis, interstitial lung disease, bronchitis; sarcoidosis, idiopathic pulmonary fibrosis, bronchiectasis, bronchiolitis, etc.
  • the present disclosure provides methods for treating respiratory virus- induced exacerbation of a chronic lung disease, where the methods involve administering an effective amount of an GFR antagonist in monotherapy, or administering, in combined effective amounts, an GFR antagonist and at least one additional therapeutic agent.
  • a “pharmaceutically acceptable excipient,” “pharmaceutically acceptable diluent,” “pharmaceutically acceptable carrier,” and “pharmaceutically acceptable adjuvant” means an excipient, diluent, carrier, and adjuvant that are useful in preparing a pharmaceutical composition that are generally safe, non-toxic and neither biologically nor otherwise undesirable, and include an excipient, diluent, carrier, and adjuvant that are acceptable for veterinary use as well as human pharmaceutical use.
  • “A pharmaceutically acceptable excipient, diluent, carrier and adjuvant” as used in the specification and claims includes one and more than one such excipient, diluent, carrier, and adjuvant.
  • (iii) is from about 13 years to about 19 years of age
  • (v) is from about 30 years to about 50 years of age
  • Item 14 The method of any one of items 1 to 10, wherein the GFR antagonist is an inhibitor of via phosphoinositide 3 kinase [PI3K] and protein kinase B (AKT) mTORCi signalling (Pl3K-AKT-mT0R inhibitor).
  • Item 15 The method of item 14, wherein the Pl3K-AKT-mT0R inhibitor is preferably selected from a compound that exhibits an IC50 with respect to Pl3K-AKT-mT0R signalling, of no more than about 100 mM or not more than about 50 pM as measurable by preferably a PI3K- AKT-mTOR enzyme inhibitory assay.
  • Item 16 The method of item 15, wherein the Pl3K-AKT-mT0R inhibitor is an PI3K inhibitor and is a small molecule which is an isoform-selective inhibitor of PI3K selected among the following compounds: BYL719 (Alpelisib, Novartis), GDC-0032 (Taselisib, Genentech/Roche), BKM120 (Buparlisib), Dactolisib (BEZ235), INK1117 (Millenium), A66 (University of Auckland), GSK260301 (Glaxosmithkline), KGN- 193 (Astra-Zeneca), TGX221 (Monash University), TG1202, CAL101 (Idelalisib, Gilead Sciences), GS-9820 (Gilead Sciences), AMG319 (Amgen), SF-1126, IC87114 (Icos Corporation), Fimepinostat (CUDC-907), BAY80- 6946 (Copan
  • Item 20 The method of any one of the preceding items, wherein the GFR antagonist is a multi-kinase inhibitor.
  • Item 23 The method of any one of items 1 to 12, or 14 or 15, wherein the GFR antagonist is an inhibitoiy nucleic acid that reduces the level of GFR, or a downstream component of GFR signalling, produced in a cell.
  • Item 24 The method of any one of items 1 to 10, wherein the GFR antagonist is selected from the group consisting of pictilisib, omipalisib, RO5126766, lonafarnib and sorafenib; or is combination of any of the aforementioned compounds.
  • Item 31 The method of any one of items 1 to 30, further comprising administering at least one additional therapeutic agent to the subject.
  • Item 39 The pharmaceutical composition for use of item 38, wherein the treatment or prevention comprises the administration of a therapeutically effective amount of the pharmaceutical composition to the subject.
  • the term typically indicates deviation from the indicated numerical value by ⁇ 20%, ⁇ 15%, ⁇ 10%, and for example ⁇ 5%.
  • the specific such deviation for a numerical value for a given technical effect will depend on the nature of the technical effect.
  • a natural or biological technical effect may generally have a larger such deviation than one for a man-made or engineering technical effect.
  • the specific such deviation for a numerical value for a given technical effect will depend on the nature of the technical effect.
  • a natural or biological technical effect may generally have a larger such deviation than one for a man-made or engineering technical effect.
  • FIG. 3 Correlation map of all detected phospho-proteins indicating Euclidean distance between proteins. To determine correlation, Z-scores of phospho-peptides and total protein levels were added and all peptide values for one protein collapsed into an average Z score. Correlation clustering was performed by Euclidean distance on combined Z scores for all conditions. Red dashed line indicates main clusters found and identified.
  • B Reactome pathway enrichment of proteins found in Cluster I in (A). Shown are the number of proteins identified in the respective cluster versus statistical significance of enrichment.Circles are increasingly sized according to the number of proteins found in the pathway.
  • C Scatter plot showing fold changes of phospho-peptides compared to fold changes of total protein levels.
  • the yellow oval indicates peptides for which phosphorylation is not driven by changes in protein abundance.
  • D Reactome pathways found enriched in Cluster II in (A). Analyses and presentation as in (B).
  • E Scatter plot showing correlation between fold changes of phosphopeptides compared to fold changes of total proteins levels. Two subsets of phosphopeptides were detected: one was mainly regulated by differential modification (indicated in yellow), the second by changes in protein abundance.
  • F STRING network analysis of proteins decreased in total protein levels ( Figure lC). Inserts indicate pathways found in the network.
  • FIG. 5 Drug-target phosphoprotein network analysis identifies growth factor signaling as central hub for possible intervention by repurposed drugs.
  • A Proteins significantly increased in phosphorylation (FC > 1, FDR ⁇ 0.05) were subjected to ReactomeFI pathway analysis and overlaid with a network of FDA-approved drugs. The network was filtered for drugs and drug targets only, to identify pathways that could be modulated by drug repurposing. Red lines indicate drug-target interactions, grey lines protein-protein interactions. Identified drugs are represented with yellow rectangles, while proteins are represented by blue circles.
  • B Search across all proteins with significant phosphorylation changes upon SARS-CoV- 2 infection for proteins related to the EGFR pathway.
  • Extracted proteins were digested and split to 1) carry out whole-cell proteomics of a tandem mass tag (TMT) 10-plex samples using liquid chromatography synchronous precursor selection mass spectromety (LC-SPS-MS3), or 2) use Fe-NTA phosphopeptide enrichment (achieving 98% enrichment) for phospho proteome analyses of a TMT 10-plex analyzed by LC-MS2.
  • TMT tandem mass tag
  • LC-SPS-MS3 liquid chromatography synchronous precursor selection mass spectromety
  • Fe-NTA phosphopeptide enrichment achieving 98% enrichment
  • the inventors identified and quantified 7,150 proteins and 15,392 different phosphopeptides for a total of 15,040 different modification sites (Figure lB, C). The main fraction of phosphopeptides were modified serines (86.4%), followed by threonine (13.4%), and tyrosine (0.2%) ( Figure lD).
  • 2,197 and 799 phosphopeptides significantly increased or decreased respectively, with a log2FC
  • Example 2 Phosphorylation of SARS-C0V-2 viral proteins in the host cell
  • SARS-C0V-1 protein 6 was described as a non-structural and possible determinant of virulence, since it accelerates infections in murine systems (Tangudu et ah, 2007). It was found that a single phosphorylation of the SARS-C0V-2 protein homologue non- structural protein 6 in host cells (Figure 2C), possibly influencing its trafficking or interaction profile. Protein 9b was also found to be modified at two sites ( Figure 2D), however the function of protein 9b in SARS-C0V-1 or SARS-C0V-2 remains unknown. Polyprotein lb is a large 7,096 amino acid protein with various functional domains.
  • Human Caco-2 (Caucasian male) cells, derived from colon carcinoma, was obtained from the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ; Braunschweig, Germany). Cells were grown at 37°C in Minimal Essential Medium (MEM) supplemented with 10% fetal bovine serum (FBS) and containing 100 IU/ml penicillin and 100 pg/ml streptomycin. All culture reagents were purchased from Sigma.
  • MEM Minimal Essential Medium
  • FBS fetal bovine serum
  • IC50 values were generated by OriginPro 2020 together with metrics for curve fits.
  • the 20 most intense precursors with a charge state between 2 and 6 per full scan were selected for fragmentation (“Top 20”) and isolated with a quadrupole isolation window of 0.7 Th.
  • MS2 scans were performed in the Ion trap (Turbo) using a maximum injection time of 50ms, AGC target value of 1.5 x 10 4 and fragmented using CID with a normalized collision energy (NCE) of 35%.
  • SPS-MS3 scans for quantification were performed on the 10 most intense MS2 fragment ions with an isolation window of 0.7 Th (MS) and 2 m/z (MS2).
  • Ions were fragmented using HCD with an NCE of 65% and analyzed in the Orbitrap with a resolution of 50,000 at m/z 200, scan range of 110-500 m/z, AGC target value of 1.5 xio 5 and a maximum injection time of 120ms. Repeated sequencing of already acquired precursors was limited by setting a dynamic exclusion of 45 seconds and 7 ppm and advanced peak determination was deactivated.
  • MS2 scans were performed in the Orbitrap using a resolution of 50,000 at m/z 200, maximum injection time of 86ms and AGC target value of 1 x 10 5 . Repeated sequencing of already acquired precursors was limited by setting a dynamic exclusion of 60 seconds and 7 ppm and advanced peak determination was deactivated.
  • Z-scores were calculated for each phospho-site and the total protein levels individually. Phosphosites were collapsed by average. For merging phosphorylation and total protein levels Z-scores for collapsed phosphorylation and protein level were added for each condition and replicate. Thus, both negative Z-scores (downregulation) will produce a lower combined Z-score and vice versa two positive Z-scores will produce a larger combined Z-score.
  • Euclidean distance correlation for all possible protein-protein pairs were calculated, taking all conditions and replicates individually into account. Heatmap was then build by Euclidean distance hierarchical clustering of correlation matrix.
  • Pathway enrichment analysis was performed by ReactomeFI cytoscape plugin or by STRING functional enrichment analysis. Both analysis used Reactome database for pathway annotations.

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  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
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  • Communicable Diseases (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un traitement de maladies virales causées par un virus de la famille des Coronaviridae par antagonisation de constituants en aval de la signalisation de récepteur de facteur de croissance (GFR). L'invention concerne certains composés connus qui sont identifiés comme candidats et sont à nouveau visés pour être utiles dans des traitements antiviraux de l'invention. Est divulguée l'application médicale des médicaments reciblés identifiés, des kits thérapeutiques et des compositions pharmaceutiques comprenant les composés.
PCT/EP2021/060672 2020-04-24 2021-04-23 Traitement d'infections par un coronavirus WO2021214296A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115400122A (zh) * 2022-04-29 2022-11-29 佛山病原微生物研究院 一种tak-632在制备用于抗腺病毒感染的药物中的用途
WO2023084489A1 (fr) * 2021-11-15 2023-05-19 Pfizer Inc. Procédés de traitement de la maladie à coronavirus 2019
CN116570599A (zh) * 2023-07-04 2023-08-11 四川大学华西医院 Vs6766联合lxh254的应用及药物组合物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014056894A1 (fr) * 2012-10-08 2014-04-17 Westfaelische Wilhelms-Universitaet Muenster Inhibiteurs de mek dans le traitement de maladies virales

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014056894A1 (fr) * 2012-10-08 2014-04-17 Westfaelische Wilhelms-Universitaet Muenster Inhibiteurs de mek dans le traitement de maladies virales

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
"Pharmaceutical Dosage Forms and Drug Delivery Systems", 1999, LIPPINCOTT, WILLIAMS, & WILKINS
A. GENNARO: "Remington: The Science and Practice of Pharmacy", 2000, LIPPINCOTT, WILLIAMS, & WILKINS
HUBERT HONDERMARCK ET AL: "The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID-19?", FASEB BIOADVANCES, vol. 2, no. 5, 9 April 2020 (2020-04-09), pages 296 - 303, XP055726926, ISSN: 2573-9832, DOI: 10.1096/fba.2020-00015 *
JASON KINDRACHUK ET AL: "Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 59, no. 2, 1 February 2015 (2015-02-01), US, pages 1088 - 1099, XP055726785, ISSN: 0066-4804, DOI: 10.1128/AAC.03659-14 *
LEIF PETERSON: "In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME", CHEMRXIV, 23 April 2020 (2020-04-23), pages 1 - 29, XP055726980, Retrieved from the Internet <URL:https://www.ssrn.com/abstract=3580951> [retrieved on 20200902], DOI: 10.2139/ssrn.3580951 *
NISHA KURIAN ET AL: "Dual Role For A MEK Inhibitor As A Modulator Of Inflammation And Host Defense Mechanisms With Potential Therapeutic Application In COPD", INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, vol. Volume 14, 26 November 2019 (2019-11-26), pages 2611 - 2624, XP055727885, DOI: 10.2147/COPD.S211619 *
SARAHS CHERIAN ET AL: "Perspectives for repurposing drugs for the coronavirus disease 2019", INDIAN JOURNAL OF MEDICAL RESEARCH, vol. 151, no. 0, 1 February 2020 (2020-02-01), IN, pages 160 - 171, XP055727615, ISSN: 0971-5916, DOI: 10.4103/ijmr.IJMR_585_20 *
THANIGAIMALAI PILLAIYAR ET AL: "Recent discovery and development of inhibitors targeting coronaviruses", DRUG DISCOVERY TODAY, vol. 25, no. 4, 1 April 2020 (2020-04-01), AMSTERDAM, NL, pages 668 - 688, XP055720906, ISSN: 1359-6446, DOI: 10.1016/j.drudis.2020.01.015 *
ZUMLA ALIMUDDIN ET AL: "Coronaviruses - drug discovery and therapeutic options", NATURE REVIEWS DRUG DISCOVERY, NATURE PUBLISHING GROUP, GB, vol. 15, no. 5, 12 February 2016 (2016-02-12), pages 327 - 347, XP037065530, ISSN: 1474-1776, [retrieved on 20160212], DOI: 10.1038/NRD.2015.37 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023084489A1 (fr) * 2021-11-15 2023-05-19 Pfizer Inc. Procédés de traitement de la maladie à coronavirus 2019
CN115400122A (zh) * 2022-04-29 2022-11-29 佛山病原微生物研究院 一种tak-632在制备用于抗腺病毒感染的药物中的用途
CN116570599A (zh) * 2023-07-04 2023-08-11 四川大学华西医院 Vs6766联合lxh254的应用及药物组合物
CN116570599B (zh) * 2023-07-04 2023-10-20 四川大学华西医院 Vs6766联合ly3009120的应用及药物组合物

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