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Principal Investigator: Hongpeng Jia
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2021
Award: $202,068
Funding agency: National Institute of Allergy and Infectious Diseases
Summary of the Funded Parent Grant (1R21AI149321-01, 01/01/2020 - 12/31/2021)
Pneumonia and associated inflammatory lung diseases (ILD) are a leading cause of death among children
and elderly worldwide and a significant source of morbidity and mortality among hospitalized patients.
Interestingly, the diseases are associate with over-activation of the renin-angiotensin system and impaired
ACE2 activity. The overall goal of present study will validate the therapeutic benefits of a newly discovered
class of ACE2 activators, named H4, in bacterial pneumonia associated inflammatory lung disease.
The immediate objectives of this application are: 1) To explore the mechanisms by which H4 and its
prodrugs buffer RAS over-activity; 2) To evaluate the efficacy of and strategies for H4 and its prodrugs to
reverse the development of bacterial pneumonia by limiting neutrophilic lung inflammation.
This project is highly significant because ILD are associated with many infectious and non-infectious lung
diseases, in which, many of them are projected to remain the leading cause of death. Therefore, not only our
research will lead to the validation of a new therapy but we will assess the impact of that treatment for
inflammatory lung diseases.
These studies will make a significant pre-clinical insight of a novel ACE2 activator, h4 and its pro-
drug in preventing and treating inflammatory lung diseases.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><ACE2><Administrative Supplement><Affect><Angiotensin Receptor><Animal Model><Animal Models and Related Studies><Applications Grants><Bacterial Pneumonia><Binding><Binding Proteins><Biology><Biomedical Engineering><Blood Neutrophil><Blood Plasma><Blood Polymorphonuclear Neutrophil><Buffers><COVID-19><COVID-19 S protein><COVID-19 outbreak><COVID-19 pathogenesis><COVID-19 prevention><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 therapy><COVID-19 treatment><COVID-19 virus><COVID19><COVID19 S protein><COVID19 outbreak><COVID19 pathogenesis><COVID19 prevention><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 therapy><COVID19 treatment><COVID19 virus><CV-19><CV19><Cause of Death><Cell Body><Cell membrane><Cells><Child><Child Youth><Children (0-21)><Closure by Ligation><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Coronavirus glycoprotein S><Coronavirus spike protein><Cytoplasmic Membrane><Data><Development><Disease><Disorder><Drug Precursors><Elderly><FIV><FTLV><Feline Immunodeficiency Virus><Feline T-Lymphotropic Lentivirus><Feline T-Lymphotropic Virus><Filament><Funding><Future><Genes><Genetic><Genotype><Goals><Grant Proposals><Host Defense><Human><Immune response><Immunological response><Impairment><Inflammatory><Inflammatory Response><Knock-out><Knockout><Ligand Binding Protein><Ligand Binding Protein Gene><Ligation><Light><Lung Inflammation><Lung damage><Lung diseases><Marrow Neutrophil><Membrane><Methodology><Mice><Mice Mammals><Mission><Modern Man><Molecular><Molecular Interaction><Morbidity><Morbidity - disease rate><Murine><Mus><NIAID><Names><Nanotechnology><National Institute of Allergy and Infectious Disease><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Pathogenesis><Patients><Pharmacology><Photoradiation><Physiologic><Physiological><Plasma><Plasma Membrane><Plasma Serum><Play><Pneumonia><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Preventive><Pro-Drugs><Prodrugs><Protein Binding><Proteins><Pulmonary Diseases><Pulmonary Disorder><Reagent><Receptor Protein><Renin-Angiotensin System><Research><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Reticuloendothelial System, Serum, Plasma><Role><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 inhibitor><SARS-CoV-2 outbreak><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 outbreak><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 inhibitor><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Source><System><Testing><Therapeutic><Validation><Viral><Virulence><Virus><Wuhan coronavirus><advanced age><airway epithelium><angiotensin converting enzyme 2><angiotensin converting enzyme II><bacteria pneumonia><bio-engineered><bio-engineers><bioengineering><block SARS-CoV-2><block severe acute respiratory syndrome coronavirus 2><bound protein><clinical practice><clinical relevance><clinically relevant><combat><corona virus disease 2019><coronavirus S protein><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 outbreak><coronavirus disease 2019 pathogenesis><coronavirus disease 2019 prevention><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 virus><coronavirus spike glycoprotein><developmental><disease of the lung><disorder of the lung><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><elders><evaluate efficacy><examine efficacy><geriatric><hCoV19><host response><immune system response><immunoresponse><improved><inflammatory lung disease><inhibit SARS-CoV-2><inhibit severe acute respiratory syndrome coronavirus 2><insight><late life><later life><lung disorder><lung injury><membrane structure><model of animal><model organism><mortality><mouse model><murine model><nCoV2><nano tech><nano technology><nano-technological><nanotech><nanotechnological><neutrophil><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><older adult><older person><parent grant><pathogen><plasmalemma><pneumocyte><pre-clinical><preclinical><prevent><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><preventing><promoter><promotor><receptor><recombinase><senior citizen><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><severe acute respiratory syndrome-CoV><social role><tool><treat COVID-19><treat COVID19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><virology><youngster>