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1.
PLoS One ; 16(9): e0257784, 2021.
Article in English | MEDLINE | ID: covidwho-1440991

ABSTRACT

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature'-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.


Subject(s)
COVID-19/drug therapy , Drug Repositioning/methods , SARS-CoV-2/genetics , Antiviral Agents/therapeutic use , Drug Evaluation, Preclinical/methods , Epithelial Cells/drug effects , Epithelium/drug effects , Humans , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/virology , Respiratory System/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
2.
PLoS One ; 16(9): e0257165, 2021.
Article in English | MEDLINE | ID: covidwho-1435607

ABSTRACT

BACKGROUND: The burden of the COVID-19 pandemic in Peru has led to people seeking alternative treatments as preventives and treatment options such as medicinal plants. This study aimed to assess factors associated with the use of medicinal plants as preventive or treatment of respiratory symptom related to COVID-19 during the pandemic in Cusco, Peru. METHOD: A web-based cross-sectional study was conducted on general public (20- to 70-year-old) from August 31 to September 20, 2020. Data were collected using a structured questionnaire via Google Forms, it consisted of an 11-item questionnaire that was developed and validated by expert judgment using Aiken's V (Aiken's V > 0.9). Both descriptive statistics and bivariate followed by multivariable logistic regression analyses were conducted to assess factors associated with the use of medicinal plants for COVID-19 prevention and respiratory symptom treatment during the pandemic. Prevalence ratios (PR) with 95% Confidence Interval (CI), and a P-value of 0.05 was used to determine statistical significance. RESULTS: A total of 1,747 respondents participated in the study, 80.2% reported that they used medicinal plants as preventives, while 71% reported that they used them to treat respiratory symptoms. At least, 24% of respondents used medicinal plants when presenting with two or more respiratory symptoms, while at least 11% used plants for malaise. For treatment or prevention, the multivariate analysis showed that most respondents used eucalyptus (p < 0.001 for both), ginger (p < 0.022 for both), spiked pepper (p < 0.003 for both), garlic (p = 0.023 for prevention), and chamomile (p = 0.011 for treatment). The respondents with COVID-19 (p < 0.001), at older ages (p = 0.046), and with a family member or friend who had COVID-19 (p < 0.001) used more plants for prevention. However, the respondents with technical or higher education used less plants for treatment (p < 0.001). CONCLUSION: There was a significant use of medicinal plants for both prevention and treatment, which was associated with several population characteristics and whether respondents had COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Plants, Medicinal , Respiratory System/drug effects , Surveys and Questionnaires , Adult , Aged , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Peru/epidemiology , Young Adult
3.
Antiviral Res ; 192: 105115, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275131

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1ß, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option.


Subject(s)
COVID-19/drug therapy , Hydrazines/pharmacology , SARS-CoV-2/drug effects , Triazoles/pharmacology , Active Transport, Cell Nucleus/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/pharmacology , COVID-19/virology , Chlorocebus aethiops , Cytokines , Ferrets , Humans , Karyopherins/antagonists & inhibitors , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Respiratory System/drug effects , Respiratory System/virology , SARS-CoV-2/metabolism , Tumor Suppressor Proteins/metabolism , Vero Cells , Virus Replication
4.
PLoS Pathog ; 17(5): e1009229, 2021 05.
Article in English | MEDLINE | ID: covidwho-1239922

ABSTRACT

While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, while interferon stimulated genes (ISGs) were induced along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, seems central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.


Subject(s)
Camelids, New World , Coronavirus Infections/immunology , Interferon Type I/metabolism , Interferons/metabolism , Middle East Respiratory Syndrome Coronavirus/immunology , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Camelids, New World/immunology , Camelids, New World/metabolism , Camelids, New World/virology , Chlorocebus aethiops , Coronavirus Infections/metabolism , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Disease Reservoirs/veterinary , Disease Resistance/drug effects , Disease Resistance/genetics , Disease Resistance/immunology , Gene Expression Regulation , Immunity, Innate/physiology , Inflammation/immunology , Inflammation/metabolism , Inflammation/veterinary , Inflammation/virology , Interferon Type I/genetics , Interferon Type I/pharmacology , Interferons/genetics , Interferons/pharmacology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/physiology , Nasal Mucosa/drug effects , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Respiratory System/drug effects , Respiratory System/immunology , Respiratory System/metabolism , Respiratory System/virology , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects
5.
J Transl Med ; 19(1): 128, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1158209

ABSTRACT

BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. METHODS: A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. RESULTS: The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. CONCLUSION: Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213.


Subject(s)
COVID-19/diet therapy , COVID-19/diagnosis , Critical Illness/therapy , Fatty Acids, Omega-3/pharmacology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Biomarkers/blood , Blood Gas Analysis , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/mortality , COVID-19/physiopathology , Critical Illness/mortality , Dietary Supplements , Double-Blind Method , Fatty Acids, Omega-3/administration & dosage , Female , Hematocrit , Humans , Inflammation Mediators/analysis , Inflammation Mediators/blood , Iran/epidemiology , Kidney/drug effects , Kidney/physiopathology , Kidney/virology , Male , Middle Aged , Mortality , Prognosis , Respiratory System/drug effects , Respiratory System/physiopathology , Respiratory System/virology , SARS-CoV-2/drug effects , Survival Analysis , Treatment Outcome
6.
Nat Biotechnol ; 39(6): 717-726, 2021 06.
Article in English | MEDLINE | ID: covidwho-1065901

ABSTRACT

Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , RNA, Messenger/pharmacology , SARS-CoV-2/genetics , Animals , COVID-19/genetics , COVID-19/virology , CRISPR-Cas Systems/genetics , Cricetinae , Disease Models, Animal , Humans , Influenza, Human/genetics , Influenza, Human/virology , Mice , Orthomyxoviridae/drug effects , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , RNA, Messenger/genetics , RNA, Viral/genetics , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2/pathogenicity
7.
Molecules ; 26(1)2020 Dec 28.
Article in English | MEDLINE | ID: covidwho-1043025

ABSTRACT

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective was to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1 h, 48 h or continuously with 10-7 M nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-ß-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca2+, ATP and EMT were evaluated by ELISA and/or Western blotting. (3) Results: nicotine induced through α7-nAChR (i) increase in cell viability, (ii) cell proliferation, (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation, (v) EGFR/pEGFR over-expression, (vi) increase in basal Ca2+ concentration, (vii) reduction of ATP production, (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that nicotine potentiates viral infection, it is likely that nicotine is involved in SARS-CoV-2 infection and severity.


Subject(s)
COVID-19/pathology , Epithelial Cells/drug effects , Nicotine/adverse effects , Respiratory System/drug effects , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Epithelial Cells/virology , Humans , Receptors, Nicotinic/metabolism , Respiratory System/virology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Signal Transduction/drug effects , Smoking/adverse effects , alpha7 Nicotinic Acetylcholine Receptor/metabolism
8.
Nat Biotechnol ; 39(6): 705-716, 2021 06.
Article in English | MEDLINE | ID: covidwho-997913

ABSTRACT

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.


Subject(s)
COVID-19/drug therapy , Chemokine CCL3/genetics , Chemokine CCL4/genetics , Hypertension/drug therapy , Receptors, CCR1/genetics , Adult , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/complications , COVID-19/genetics , COVID-19/virology , Disease Progression , Female , Gene Expression Regulation/drug effects , Humans , Hypertension/complications , Hypertension/genetics , Hypertension/pathology , Inflammation/complications , Inflammation/drug therapy , Inflammation/genetics , Inflammation/virology , Male , Middle Aged , RNA-Seq , Respiratory System/drug effects , Respiratory System/pathology , Respiratory System/virology , Risk Factors , SARS-CoV-2/pathogenicity , Single-Cell Analysis
9.
Pharmacol Res Perspect ; 9(1): e00698, 2021 02.
Article in English | MEDLINE | ID: covidwho-986400

ABSTRACT

As the death toll of Coronavirus disease 19 (COVID-19) continues to rise worldwide, it is imperative to explore novel molecular mechanisms for targeting SARS-CoV-2. Rather than looking for drugs that directly interact with key viral proteins inhibiting its replication, an alternative and possibly add-on approach is to dismantle the host cell machinery that enables the virus to infect the host cell and spread from one cell to another. Excellent examples of such machinery are host cell proteases whose role in viral pathogenesis has been demonstrated in numerous coronaviruses. In this review, we propose two therapeutic modalities to tackle SARS-CoV-2 infections; the first is to transcriptionally modulate the expression of cellular proteases and their endogenous inhibitors and the second is to directly inhibit their enzymatic activity. We present a nonexhaustive collection of clinically investigated drugs that act by one of these mechanisms and thus represent promising candidates for preclinical in vitro testing and hopefully clinical testing in COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/enzymology , Molecular Targeted Therapy/methods , Peptide Hydrolases/metabolism , Protease Inhibitors/therapeutic use , Respiratory System/virology , SARS-CoV-2/growth & development , Humans , Protease Inhibitors/pharmacology , Respiratory System/drug effects
10.
Am J Physiol Lung Cell Mol Physiol ; 319(5): L843-L847, 2020 11 01.
Article in English | MEDLINE | ID: covidwho-809034

ABSTRACT

The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males versus females as a model, we explored the effect of estrogen versus testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared with males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.


Subject(s)
Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/metabolism , Respiratory System/metabolism , Adult , Aged , Angiotensin-Converting Enzyme 2 , COVID-19 , Cells, Cultured , Coronavirus Infections/enzymology , Estrogens/metabolism , Estrogens/pharmacology , Female , Humans , Male , Middle Aged , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/enzymology , Myocytes, Smooth Muscle/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/enzymology , Respiratory System/cytology , Respiratory System/drug effects , Respiratory System/enzymology , Sex Factors , Testosterone/metabolism , Testosterone/pharmacology
11.
Commun Biol ; 3(1): 466, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-723561

ABSTRACT

Chinese herbal formulas including the lung-cleaning and toxicity-excluding (LCTE) soup have played an important role in treating the ongoing COVID-19 pandemic (caused by SARS-CoV-2) in China. Applying LCTE outside of China may prove challenging due to the unfamiliar rationale behind its application in terms of Traditional Chinese Medicine. To overcome this barrier, a biochemical understanding of the clinical effects of LCTE is needed. Here, we explore the chemical compounds present in the reported LCTE ingredients and the proteins targeted by these compounds via a network pharmacology analysis. Our results indicate that LCTE contains compounds with the potential to directly inhibit SARS-CoV-2 and inflammation, and that the compound targets proteins highly related to COVID-19's main symptoms. We predict the general effect of LCTE is to affect the pathways involved in viral and other microbial infections, inflammation/cytokine response, and lung diseases. Our work provides a biochemical basis for using LCTE to treat COVID-19 and its main symptoms.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19 , Calcium Sulfate , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Drug Delivery Systems , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Gastrointestinal Tract/drug effects , Humans , Metabolic Networks and Pathways/drug effects , Phytotherapy , Plants, Medicinal/chemistry , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Respiratory System/drug effects , SARS-CoV-2 , Viral Proteins/antagonists & inhibitors
12.
IUBMB Life ; 72(10): 2097-2111, 2020 10.
Article in English | MEDLINE | ID: covidwho-696287

ABSTRACT

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Bacterial Infections/epidemiology , COVID-19/epidemiology , Pandemics , Pneumonia, Bacterial/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/pathogenicity , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Infections/virology , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Coinfection , Haemophilus influenzae/drug effects , Haemophilus influenzae/pathogenicity , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Legionella pneumophila/drug effects , Legionella pneumophila/pathogenicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/virology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , Respiratory System/drug effects , Respiratory System/microbiology , Respiratory System/pathology , Respiratory System/virology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/pathogenicity , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/pathogenicity
13.
J Am Pharm Assoc (2003) ; 60(6): e145-e152, 2020.
Article in English | MEDLINE | ID: covidwho-457074

ABSTRACT

OBJECTIVES: The current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered first-line agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection. METHODS: 1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs. RESULTS: Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. CONCLUSION: These analyses suggest that pharmacists and clinicians will need to consider the specific medication's adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/mortality , Diabetes Mellitus/drug therapy , Diabetic Nephropathies/prevention & control , Respiratory System/drug effects , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/metabolism , China/epidemiology , Diabetes Mellitus/metabolism , Diabetic Nephropathies/complications , Diabetic Nephropathies/metabolism , Humans , Morbidity/trends , Pharmacovigilance , Prevalence , Renin-Angiotensin System/drug effects , Respiratory System/metabolism , SARS-CoV-2
14.
Int J Mol Sci ; 21(11)2020 May 27.
Article in English | MEDLINE | ID: covidwho-382033

ABSTRACT

At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Fenretinide/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines , Fenretinide/pharmacology , Humans , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2 , Signal Transduction/drug effects
15.
Am J Physiol Lung Cell Mol Physiol ; 318(6): L1280-L1281, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-326936

ABSTRACT

There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections , Estrogens/pharmacology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Epithelial Cells/drug effects , Epithelial Cells/virology , Estrogens/metabolism , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2
16.
Pharmacol Res ; 157: 104881, 2020 07.
Article in English | MEDLINE | ID: covidwho-165166

ABSTRACT

The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common feature - airway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs.


Subject(s)
Granulocytes/drug effects , Respiratory System Agents/therapeutic use , Respiratory System/drug effects , Respiratory Tract Diseases/drug therapy , Animals , Chemotaxis, Leukocyte/drug effects , Granulocytes/immunology , Granulocytes/metabolism , Humans , Inflammation Mediators/metabolism , Molecular Targeted Therapy , Phenotype , Respiratory System/immunology , Respiratory System/metabolism , Respiratory System/physiopathology , Respiratory System Agents/adverse effects , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/metabolism , Respiratory Tract Diseases/physiopathology , Signal Transduction
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