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1.
Drug Des Devel Ther ; 15: 1213-1223, 2021.
Article in English | MEDLINE | ID: covidwho-1181234

ABSTRACT

Severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) is an emerging pathogen, which is similar to previous SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) occurrences. However, we only get few understandings about the pathogenesis of SARS-CoV-2, which need to further be studied. The discovery of an agent that has a treatment efficacy against SARS-CoV-2 is very urgent. In this review, we briefly discuss the virology of this pathogen and focus on the available understanding of the pathogenesis and treatments of this pathogen including the uses of nucleoside analogues, protease inhibitors, interferons, and other small-molecule drugs, on the basis previous comprehensions of SARS and MERS. These reviewed concepts may be beneficial in providing new insights and potential treatments for COVID-19.


Subject(s)
Antiviral Agents/pharmacology , /drug effects , /physiology , Antiviral Agents/therapeutic use , /antagonists & inhibitors , Humans , /pathogenicity
2.
Clin Sci (Lond) ; 134(21): 2851-2871, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-1177131

ABSTRACT

Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/enzymology , Receptors, Virus/metabolism , Virus Internalization , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protein Conformation , Receptors, Virus/chemistry , Structure-Activity Relationship
3.
Orv Hetil ; 162(17): 643-651, 2021 04 10.
Article in Hungarian | MEDLINE | ID: covidwho-1175459

ABSTRACT

Összefoglaló. Az új típusú koronavírus-fertozés (COVID-19) nagy terhet ró az egészségügyi ellátórendszerre és a társadalomra. A betegségnek három nagy szakasza van, melyek alapvetoen meghatározzák a kezelést. Az I-IIA fázisban az antivirális, míg a IIB-III. fázisban a gyulladásgátló kezelés áll elotérben, melyhez intenzív terápiás, szupportív kezelés csatlakozik. A jelen ajánlás kizárólag a gyógyszeres kezelésre vonatkozik, és a rendelkezésre álló bizonyítékok alapján foglalja össze a terápiás lehetoségeket. Emellett egy javasolt kezelési algoritmust is tartalmaz. Orv Hetil. 2021; 162(17): 643-651. Summary. The novel coronavirus infection (COVID-19) places a heavy burden on the health care system and our society. There are three major stages in the disease that fundamentally determine treatment approaches. Phases I-IIA require primarily antiviral treatment. In phases IIB-III, anti-inflammatory treatment is needed accompanied by intensive and supportive care. This recommendation applies only to pharmacotherapy and summarizes the therapeutic options based on the available evidence. It also includes a proposed treatment algorithm. Orv Hetil. 2021; 162(17): 643-651.


Subject(s)
Anti-Inflammatory Agents , Antiviral Agents , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , /epidemiology , Humans
5.
Can Fam Physician ; 67(3): 171-179, 2021 03.
Article in English | MEDLINE | ID: covidwho-1168518

ABSTRACT

OBJECTIVE: To keep health care providers, in response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, informed about the medications that have been proposed to treat the disease and the evidence supporting their use. QUALITY OF EVIDENCE: A narrative review of medications most widely used to treat COVID-19 was conducted, outlining the best available evidence for each pharmacologic treatment to date. Searches were performed in PubMed, EMBASE, and MEDLINE using key words COVID-19 and treatment, as well as related terms. Relevant research studies conducted in human populations and cases specific to patients with COVID-19 were included, as were relevant hand-searched papers and reviews. Only articles in English and Chinese were included. MAIN MESSAGE: While current management of patients with COVID-19 largely involves supportive care, without a widely available vaccine, practitioners have also resorted to repurposing medications used for other indications. This has caused considerable controversy, as many of these treatments have limited clinical evidence supporting their use and therefore pose implications for patient safety, drug access, and public health. For instance, medications such as hydroxychloroquine and chloroquine, lopinavir-ritonavir, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers gained widespread media attention owing to hype, misinformation, or misinterpretation of research evidence. CONCLUSION: Given the severity of the pandemic and the potential broad effects of implementing safe and effective treatment, this article provides a narrative review of the current evidence behind the most widely used medications to treat COVID-19 in order to enable health care practitioners to make informed decisions in the care of patients with this life-threatening disease.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , Evidence-Based Medicine , Immunoglobulins/therapeutic use , Chloroquine/therapeutic use , Drug Therapy, Combination , Humans , Hydroxychloroquine/therapeutic use
6.
Saudi Med J ; 42(4): 355-362, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1168261

ABSTRACT

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and viral pneumonia in pediatrics worldwide. In the Kingdom of Saudi Arabia (KSA), the prevalence of RSV is 23.5% in pediatric patients with acute lower respiratory tract illness. Coronavirus disease (COVID-19) poses critical public health and socioeconomic challenges in KSA. The Saudi Pediatric Pulmonology Association (SPPA), a subsidiary of the Saudi Thoracic Society (STS), developed a task force to determine the potential challenges and barriers to the RSV immunoprophylaxis program during the era of COVID-19 and to compose a practical, nationwide, and multidisciplinary approach to address these challenges. Some of the recommendations to manage these challenges include increasing the number of RSV immunoprophylaxis clinics, drive-thru visits, home-care services, and swift referrals to the RSV immunoprophylaxis program specialists. Additional training is required for healthcare personnel to add RSV immunoprophylaxis to the regular immunization schedule.


Subject(s)
Antiviral Agents/therapeutic use , Bronchiolitis, Viral/prevention & control , Delivery of Health Care/methods , Immunization Programs/methods , Palivizumab/therapeutic use , Respiratory Syncytial Virus Infections/prevention & control , Advisory Committees , /prevention & control , Home Care Services , Humans , Infant , Infant, Newborn , Injections , Pulmonary Medicine , Saudi Arabia , Societies, Medical
7.
Br J Hosp Med (Lond) ; 82(3): 1-9, 2021 Mar 02.
Article in English | MEDLINE | ID: covidwho-1168180

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies.


Subject(s)
Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Glucocorticoids/therapeutic use , Immunologic Factors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/therapeutic use , Colchicine/therapeutic use , Dexamethasone/therapeutic use , Humans , Immunization, Passive , Ivermectin/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use
8.
Mol Med Rep ; 23(5)2021 May.
Article in English | MEDLINE | ID: covidwho-1167801

ABSTRACT

Although the COVID­19 epidemic has lasted for months, it has not yet been successfully controlled, and little is known about neonatal COVID­19. Therefore, literature search was conducted for references in PubMed, Science Direct, ProQuest, Web of Science and China National Knowledge Infrastructure for detailed case reports on neonatal COVID­19 published as of July 15, 2020, to facilitate the clinical treatment, epidemic prevention and control of neonatal COVID­19. Forty nonoverlapping case reports focusing mainly on the demographic characteristics, transmission modes, clinical features, treatments and prognosis of neonatal COVID­19, including 3 in Chinese and 37 in English, were available.


Subject(s)
/pathology , /physiology , Antibodies, Viral/analysis , Antiviral Agents/therapeutic use , Asymptomatic Diseases , /transmission , Humans , Infant, Newborn , Milk, Human/virology , RNA, Viral/metabolism , /immunology , Thorax/diagnostic imaging
9.
Clin Microbiol Rev ; 34(3)2021 06 16.
Article in English | MEDLINE | ID: covidwho-1166352

ABSTRACT

Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.


Subject(s)
DNA Viruses , Lung Injury , RNA Viruses , Respiratory Tract Infections , Virus Diseases , Adult , Aged , Antiviral Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Interferons/therapeutic use , Lung/immunology , Lung/virology , Lung Injury/diagnosis , Lung Injury/drug therapy , Lung Injury/immunology , Lung Injury/virology , Male , Middle Aged , Pandemics
11.
J Pharm Pharmacol ; 73(3): 281-299, 2021 Mar 06.
Article in English | MEDLINE | ID: covidwho-1165435

ABSTRACT

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.


Subject(s)
Antiviral Agents/immunology , Antiviral Agents/therapeutic use , /immunology , Immunologic Factors/therapeutic use , Propolis/immunology , Propolis/therapeutic use , Animals , Humans , Immunologic Factors/immunology , /immunology
12.
J Gen Virol ; 102(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1160599

ABSTRACT

Coronavirus protease nsp5 (Mpro, 3CLpro) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.


Subject(s)
Antiviral Agents/therapeutic use , /antagonists & inhibitors , /enzymology , Viral Nonstructural Proteins/antagonists & inhibitors , /therapeutic use , Amino Acid Sequence , Coronavirus/enzymology , Coronavirus/metabolism , /metabolism , Humans , Phylogeny , Viral Nonstructural Proteins/metabolism
13.
Cir Cir ; 89(2): 269-274, 2021.
Article in English | MEDLINE | ID: covidwho-1158505

ABSTRACT

ANTECEDENTES: En diciembre de 2019 se identificó en la ciudad de Wuhan, China, un nuevo beta coronavirus, el SARS-CoV-2, como agente causal de neumonía grave, conocida como COVID-19, lo cual ha provocado medidas estrictas de aislamiento, cierre de programas de trasplante hepático y la necesidad de modificar los protocolos de tratamiento. OBJETIVO: Documentar la información publicada sobre el impacto de la COVID-19 en la población con antecedente de trasplante hepático y establecer un protocolo de tratamiento. MÉTODO: Se buscaron en PubMed los términos MeSH "SARS-CoV-2", "COVID-19", "trasplante hepático" y "tratamiento". RESULTADOS: Hasta el momento se ha demostrado en la población con trasplante hepático una mayor facilidad para adquirir el virus, sin una diferencia en la mortalidad al compararla con la población general. La inmunosupresión debe continuar, sin suspender los inhibidores de la calcineurina. Del tratamiento específico, los esteroides son los que han demostrado el mayor beneficio clínico y una disminución de la mortalidad. CONCLUSIÓN: El trasplante hepático no se asocia de manera independiente a una mayor mortalidad. Otros factores, además del trasplante, deben tomarse en cuenta al momento de establecer la gravedad. BACKGROUND: In December 2019, a new beta coronavirus, SARS-CoV-2, was identified in the city of Wuhan, China, as a causative agent of severe pneumonia, known as COVID-19, which has led to strict isolation measures, closure of liver transplantation programs and the need to modify treatment protocols. OBJECTIVE: Document the information published so far on the impact of COVID-19 in the population with a history of liver transplantation and establish a treatment protocol. METHOD: MeSH terms were searched for "SARS-CoV-2", "COVID-19", "liver transplantation" and "treatment". RESULTS: Up to now, a greater ease in acquiring the virus has been shown in the liver transplant population, without a difference in mortality when compared to the general population. Immunosuppression should continue at the minimum tolerated levels, without suspending calcineurin inhibitors. Of the specific treatment, steroids are those that have shown the greatest clinical benefit and decreased mortality. CONCLUSION: Liver transplantation is not independently associated with higher mortality. Factors other than transplantation must be taken into account when considering the risk of severity.


Subject(s)
/epidemiology , Immunocompromised Host , Liver Transplantation , Pandemics , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Blood Component Transfusion , /transmission , Graft Rejection/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Immunosuppressive Agents/administration & dosage , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Waiting Lists , Withholding Treatment
14.
Virol J ; 18(1): 66, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1158210

ABSTRACT

Beginning in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel pathogen that causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 has infected more than 111 million people worldwide and caused over 2.47 million deaths. Individuals infected with SARS-CoV-2 show symptoms of fever, cough, dyspnea, and fatigue with severe cases that can develop into pneumonia, myocarditis, acute respiratory distress syndrome, hypercoagulability, and even multi-organ failure. Current clinical management consists largely of supportive care as commonly administered treatments, including convalescent plasma, remdesivir, and high-dose glucocorticoids. These have demonstrated modest benefits in a small subset of hospitalized patients, with only dexamethasone showing demonstrable efficacy in reducing mortality and length of hospitalization. At this time, no SARS-CoV-2-specific antiviral drugs are available, although several vaccines have been approved for use in recent months. In this review, we will evaluate the efficacy of preclinical and clinical drugs that precisely target three different, essential steps of the SARS-CoV-2 replication cycle: the spike protein during entry, main protease (MPro) during proteolytic activation, and RNA-dependent RNA polymerase (RdRp) during transcription. We will assess the advantages and limitations of drugs that precisely target evolutionarily well-conserved domains, which are less likely to mutate, and therefore less likely to escape the effects of these drugs. We propose that a multi-drug cocktail targeting precise proteins, critical to the viral replication cycle, such as spike protein, MPro, and RdRp, will be the most effective strategy of inhibiting SARS-CoV-2 replication and limiting its spread in the general population.


Subject(s)
Antiviral Agents/therapeutic use , /drug effects , Animals , Antiviral Agents/pharmacology , /therapy , /administration & dosage , Humans , Immunization, Passive , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , Virus Replication/drug effects
18.
Euro Surveill ; 26(9)2021 03.
Article in English | MEDLINE | ID: covidwho-1154190

ABSTRACT

BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.


Subject(s)
Antiviral Agents/therapeutic use , /epidemiology , Chloroquine/adverse effects , Female , Humans , Hydroxychloroquine/adverse effects , Incidence , Male , Prospective Studies , Spain/epidemiology
19.
Ther Adv Respir Dis ; 15: 17534666211007214, 2021.
Article in English | MEDLINE | ID: covidwho-1153949

ABSTRACT

The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection. We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization, virological clearance, and severe adverse events. A total of 48 studies were retrieved from the databases. Eleven articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir. We can conclude that dexamethasone would have a better result in hospitalized patients, especially in low-resources settings. The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries, since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources.The reviews of this paper are available via the supplemental material section.


Subject(s)
Antiviral Agents/therapeutic use , Hospitalization , Humans , Treatment Outcome
20.
BMJ Case Rep ; 14(3)2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1153657

ABSTRACT

A 54-year-old woman presented with pruritic rash and hives of 3 days' duration followed by shortness of breath for 1 day. SARS-CoV-2 PCR test for COVID-19 was positive. Cutaneous manifestations of COVID-19 include acral lesions, urticarial rash, erythematous maculopapular rash, vascular rashes and vesicular rash. The cutaneous manifestations are mostly described as self-limiting. Urticarial rashes are not reported as the initial presentation symptom of COVID-19 infection but mostly noted to occur at the same time or after the onset of non-cutaneous symptoms. Management of cutaneous manifestations of COVID-19 affecting quality of life has not been well studied. Antihistamine therapy is the primary recommended therapy. Role of antiviral therapy for severe cases of rash needs to be further assessed.


Subject(s)
/complications , Exanthema/virology , Urticaria/virology , Antiviral Agents/therapeutic use , Atrial Fibrillation/complications , Exanthema/pathology , Exanthema/therapy , Female , Histamine Antagonists/therapeutic use , Humans , Hypertension, Pulmonary/complications , Middle Aged , Obesity/complications , Renal Insufficiency, Chronic/complications , Skin/pathology , Sleep Apnea, Obstructive/complications , Treatment Outcome , Urticaria/pathology , Urticaria/therapy
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