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1.
Eur J Clin Microbiol Infect Dis ; 39(6): 1021-1026, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1718753

ABSTRACT

Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Betacoronavirus/metabolism , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral , Pneumonia , SARS Virus/metabolism , Severe Acute Respiratory Syndrome , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Humans , Pneumonia/etiology , Pneumonia/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy
2.
Pharmacol Res ; 176: 106053, 2022 02.
Article in English | MEDLINE | ID: covidwho-1586872

ABSTRACT

BACKGROUND: Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. OBJECTIVES: to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. METHODS: We identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. RESULTS: No randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57-1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 - 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. CONCLUSIONS: Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/etiology , Coronavirus Infections/drug therapy , Glucocorticoids/therapeutic use , Influenza, Human/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , COVID-19/mortality , Cardiovascular Diseases/mortality , Coronavirus Infections/mortality , Hospitalization , Humans , Influenza, Human/mortality , Randomized Controlled Trials as Topic , SARS-CoV-2/drug effects
3.
Rev Med Virol ; 31(6): e2234, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574124

ABSTRACT

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Genetic Predisposition to Disease , Influenza, Human/immunology , Respiratory Syncytial Virus Infections/immunology , Severe Acute Respiratory Syndrome/immunology , Antiviral Agents/therapeutic use , Biological Variation, Individual , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/virology , Gene Expression , Humans , Immunity, Innate , Immunologic Factors/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/genetics , Influenza, Human/virology , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/immunology , Orthomyxoviridae/drug effects , Orthomyxoviridae/immunology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/drug effects , Respiratory Syncytial Viruses/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
4.
Virol J ; 17(1): 136, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-1435256

ABSTRACT

BACKGROUND: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. METHODS: To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. RESULTS: In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 µg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 µg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50µg/ml Echinaforce®. CONCLUSIONS: These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus 229E, Human/drug effects , Coronavirus Infections/drug therapy , Coronavirus/drug effects , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Animals , COVID-19 , Cell Line , Chlorocebus aethiops , Common Cold/drug therapy , Common Cold/virology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , RNA Viruses/drug effects , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology , Vero Cells
6.
Pharmacol Res Perspect ; 9(1): e00691, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384293

ABSTRACT

Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA-approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in-depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against coronaviruses infections. In this review, we discuss the virology of human coronaviruses highlighting the main biological targets and summarize the current state-of-the-art of possible therapeutic options to inhibit coronaviruses infections. We mostly focus on FDA-approved and preclinical drugs targeting viral conserved elements.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Coronavirus Infections/metabolism , Coronavirus/metabolism , Dipeptidyl Peptidase 4/metabolism , Severe Acute Respiratory Syndrome/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Antiviral Agents/administration & dosage , Antiviral Agents/metabolism , Azoles/administration & dosage , Azoles/metabolism , COVID-19/drug therapy , Coronavirus/drug effects , Coronavirus Infections/drug therapy , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/metabolism , Humans , Isoindoles , Naphthoquinones/administration & dosage , Naphthoquinones/metabolism , Organoselenium Compounds/administration & dosage , Organoselenium Compounds/metabolism , Severe Acute Respiratory Syndrome/drug therapy
7.
Immunol Res ; 69(5): 457-460, 2021 10.
Article in English | MEDLINE | ID: covidwho-1345195

ABSTRACT

In this manuscript, COVID-19, Ebola virus disease, Nipah virus infection, SARS, and MERS are suggested to be considered for a novel immunological reclassification as acute onset immune dysrhythmia syndrome (n-AIDS) due to altered monocytic, Th1/Th2, as well as cytokines and chemokines balances. n-AIDs is postulated to be the cause of the acute respiratory distress and multi-inflammatory syndromes which are described with fatal COVID-19, and immunomodulators are suggested to effectively manage the mentioned diseases as well as for other disorders caused by Th1/Th2 imbalance. Meanwhile, para COVID syndrome is suggested to describe various immune-related complications, whether before or after recovery, and to embrace a potential of a latent infection, that might be discovered later, as occurred with Ebola virus disease. Finally, our hypothesis has evolved out of our real-life practice that uses immunomodulatory drugs to manage COVID-19 safely and effectively.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Hemorrhagic Fever, Ebola/immunology , Henipavirus Infections/immunology , Acquired Immunodeficiency Syndrome/immunology , COVID-19/drug therapy , Chemokines/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Hemorrhagic Fever, Ebola/drug therapy , Henipavirus Infections/drug therapy , Humans , Immunologic Factors/therapeutic use , Lymphocytes/immunology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/immunology
8.
Am J Chin Med ; 48(7): 1539-1552, 2020.
Article in English | MEDLINE | ID: covidwho-1327716

ABSTRACT

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.


Subject(s)
COVID-19/drug therapy , Coronavirus Infections/drug therapy , Glycyrrhizic Acid/therapeutic use , Middle East Respiratory Syndrome Coronavirus/drug effects , SARS Virus/drug effects , SARS-CoV-2/drug effects , Severe Acute Respiratory Syndrome/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics , SARS Virus/physiology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/virology , Treatment Outcome
10.
Pharmacol Res ; 157: 104872, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318931

ABSTRACT

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , COVID-19 , Humans , Pandemics , SARS-CoV-2
11.
Eur J Pharmacol ; 906: 174248, 2021 Sep 05.
Article in English | MEDLINE | ID: covidwho-1267662

ABSTRACT

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Interferons/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/mortality , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Humans , Interferons/adverse effects , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/mortality
12.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1259762

ABSTRACT

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Host-Pathogen Interactions/immunology , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Dexamethasone/therapeutic use , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/drug effects , Inflammation , Interferon Type I/genetics , Interferon Type I/immunology , Interleukins/genetics , Interleukins/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Signal Transduction , Survival Analysis
13.
Neonatal Netw ; 40(3): 175-182, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1259287

ABSTRACT

The novel coronavirus disease 2019 (COVID-19), appeared in the United States over 1 year ago. This virus has a wide range of presentations, from being asymptomatic to causing severe acute respiratory syndrome, which can lead to death. It has led to a worldwide effort to find effective treatments, from repurposed medications to new discoveries, as well as the push to develop effective vaccines. As the race to fight this pandemic unfolds, this column provides what is currently available to combat this virus, how it has been utilized in the pregnant population, and what data have been made available about how these treatments affect fetal development and the neonate.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , COVID-19/transmission , Infectious Disease Transmission, Vertical/prevention & control , Maternal Health Services/standards , Neonatal Nursing/standards , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/prevention & control , Adult , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Female , Humans , Infant, Newborn , Male , Practice Guidelines as Topic , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , United States/epidemiology
14.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-1231668

ABSTRACT

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Dermatologic Agents/adverse effects , Drug Eruptions/etiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Biological Products/administration & dosage , Biological Products/adverse effects , COVID-19 , Dermatologic Agents/therapeutic use , Drug Eruptions/epidemiology , Drug Eruptions/physiopathology , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Incidence , Male , Pandemics , Prognosis , Risk Assessment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology
15.
Int J Mol Sci ; 22(9)2021 May 07.
Article in English | MEDLINE | ID: covidwho-1224028

ABSTRACT

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.


Subject(s)
COVID-19/blood , Galectins/blood , Osteopontin/blood , Pneumonia/blood , Severe Acute Respiratory Syndrome/blood , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , Biomarkers/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Humans , Inflammation/metabolism , Kidney/metabolism , Kidney/pathology , Kidney/virology , Male , Middle Aged , Pneumonia/complications , Pneumonia/drug therapy , Pneumonia/virology , ROC Curve , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Young Adult
16.
Protein J ; 39(6): 644-656, 2020 12.
Article in English | MEDLINE | ID: covidwho-1196608

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) has resulted in a global pandemic and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have suggested that a precise disulfide-thiol balance is crucial for viral entry and fusion into the host cell and that oxidative stress generated from free radicals can affect this balance. Here, we reviewed the current knowledge about the role of oxidative stress on SARS-CoV and SARS-CoV-2 infections. We focused on the impact of antioxidants, like NADPH and glutathione, and redox proteins, such as thioredoxin and protein disulfide isomerase, that maintain the disulfide-thiol balance in the cell. The possible influence of these biomolecules on the binding of viral protein with the host cell angiotensin-converting enzyme II receptor protein as well as on the severity of COVID-19 infection was discussed.


Subject(s)
COVID-19/metabolism , Oxidative Stress , SARS Virus/physiology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/metabolism , Acetylcysteine/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Discovery , Humans , Models, Molecular , Oxidative Stress/drug effects , SARS-CoV-2/drug effects , Severe Acute Respiratory Syndrome/drug therapy , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/metabolism
17.
Aging (Albany NY) ; 13(8): 10833-10852, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1196152

ABSTRACT

Coronavirus disease 2019 (COVID-19) experienced an outbreak that expanded worldwide. Lopinavir/ritonavir (LPV/r), which is used effectively for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections, was applied for COVID-19 treatment given similarities in the molecular structures of these viruses. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of lopinavir/ritonavir antiviral treatment in patients with SARS, MERS, and COVID-19. After registration with INPLASY, a search was conducted in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, WanFang Data, China Biomedical Literature Database (CBM) and other databases for all relevant literature on lopinavir/ritonavir treatment of SARS, MERS and COVID-19. The Cochrane Collaboration's bias risk assessment tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the literature, and RevMan 5.3 software was used to evaluate the relevant outcome indicators of the efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19. A total of 18 eligible studies (including randomized controlled studies, cohort studies, and case-control studies) were retrieved and included with a total of 2273 patients. The lopinavir/ritonavir group exhibited an increased nucleic acid conversion rate (P=0.004), higher virus clearance rate (P<0.0001), lower mortality rate (P=0.002), and reduced incidence of acute respiratory distress syndrome (ARDS) (P=0.02) compared with the control group. No significant benefit in the improvement rate of chest CT (P=0.08) or incidence of adverse events (P=0.45) was noted. The lopinavir/ritonavir group had a lower incidence of acute respiratory distress syndrome (P=0.02). According to the clinical prognostic results, the incidence of adverse events between the two groups was not statistically significant (P<0.0001). The efficacy of lopinavir/ritonavir in the treatment of patients with SARS, MERS and COVID-19 was significantly better than that of the control. Furthermore, the incidence of adverse events did not significantly increase. Lopinavir/ritonavir is effective in the treatment of COVID-19, and this combination should be further assessed in RCT studies. In addition, when we analyzed the differences in age and sex, we found that the differences were statistically significant in the safety and effectiveness of lopinavir/ritonavir in patients with COVID-19, and both of these factors played a significant role in the trial.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adult , Aged , COVID-19/epidemiology , COVID-19/mortality , Coronavirus Infections/drug therapy , Female , Humans , Male , Middle Aged , Severe Acute Respiratory Syndrome/drug therapy , Young Adult
19.
FASEB J ; 35(4): e21360, 2021 04.
Article in English | MEDLINE | ID: covidwho-1145195

ABSTRACT

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.


Subject(s)
Antiviral Agents/pharmacology , Berberine/pharmacology , COVID-19 , Gene Expression Regulation/drug effects , Models, Biological , SARS Virus/metabolism , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome , Administration, Oral , COVID-19/drug therapy , COVID-19/metabolism , Cell Line , Computer Simulation , Humans , Pandemics , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/metabolism
20.
Molecules ; 26(6)2021 Mar 21.
Article in English | MEDLINE | ID: covidwho-1143540

ABSTRACT

Since the emergence of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) first reported in Wuhan, China in December 2019, COVID-19 has spread to all the continents at an unprecedented pace. This pandemic has caused not only hundreds of thousands of mortalities but also a huge economic setback throughout the world. Therefore, the scientific communities around the world have focused on finding antiviral therapeutic agents to either fight or halt the spread of SARS-CoV-2. Since certain medicinal plants and herbal formulae have proved to be effective in treatment of similar viral infections such as those caused by SARS and Ebola, scientists have paid more attention to natural products for effective treatment of this devastating pandemic. This review summarizes studies and ethnobotanical information on plants and their constituents used for treatment of infections caused by viruses related to the coronavirus family. Herein, we provide a critical analysis of previous reports and how to exploit published data for the discovery of novel therapeutic leads to fight against COVID-19.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , Plants, Medicinal/chemistry , Severe Acute Respiratory Syndrome/drug therapy , Animals , Antiviral Agents/therapeutic use , Biological Products/therapeutic use , Humans , SARS Virus/drug effects , SARS Virus/metabolism , Secondary Metabolism
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