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1.
Sci Rep ; 10(1): 16200, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004837

RESUMO

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Digoxina/farmacologia , Ouabaína/farmacologia , Replicação Viral , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Betacoronavirus/fisiologia , Chlorocebus aethiops , Cloroquina/farmacologia , Concentração Inibidora 50 , Células Vero
4.
Monaldi Arch Chest Dis ; 90(4)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33059413

RESUMO

Knowledge of treatment regimens and outcomes for novel coronavirus disease 2019 (COVID-19) is evolving. Recent studies have reported mortality rates ranging from 39-50% among hospitalized patients with COVID-19. We report our experience ofmanagement and outcomes of hospitalized patients with COVID-19 at a large tertiary-care center in Midwestern United States. Of 658 patients presenting to our tertiary care center, 217 needed hospitalization, majority (77%) of whom were severely sick requiring admission to the intensive care unit (ICU). All received corticosteroids, and 78% of the patients received tocilizumab. More than two-thirds of the patients received anticoagulation and 80% of patients in the ICU had prone-positioning. The median duration of hospitalization was 12 days (interquartile range, 8 to16), median duration of intensive care unit stay was 7 days (interquartile range, 5 to 9) and requirement of mechanical ventilation was 6 days (interquartile range, 5 to 8) in our cohort. Of the 217 patients, 27 died (12% mortality). The majority of our patients received corticosteroids, tocilizumab, anticoagulation and prone positioning. While higher mortality rates of >30% have been reported in various studies among hospitalized patients with COVID-19, the majority of hospitalized patients in our cohort survived with a low mortality rate. The majority of our patients received corticosteroids, tocilizumab, anticoagulation and prone positioning. While higher mortality rates of >30% have been reported in various studies among hospitalized patients with COVID-19, the majority of hospitalized patients in our cohort survived with a low mortality rate.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos , Hospitalização , Pneumonia Viral/terapia , Atenção Terciária à Saúde , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva , Meio-Oeste dos Estados Unidos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Respiração Artificial , Estudos Retrospectivos , Centros de Atenção Terciária
5.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

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.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
6.
Eur Rev Med Pharmacol Sci ; 24(18): 9739-9743, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33015819

RESUMO

OBJECTIVE: Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases. It has been recognized recently as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5). We aimed at determining which drugs used in dentistry interact with Remdesivir in order to avoid adverse reactions that may worsen the condition of patients with COVID-19. MATERIALS AND METHODS: A literature review was conducted to identify potential drug interactions between remdesivir (used in the treatment of COVID-19) and drugs prescribed in dentistry. The search was made in the databases PubMed and MEDLINE and official websites using key terms remdesivir, drug interactions and dentistry for articles published up to 31st July 2020. RESULTS: According to the articles reviewed, a total of 279 drugs interact with Remdesivir. Two major interactions have been reported, 277 moderate drug interactions, and one with alcohol/food. The drug interactions involving drugs prescribed in dentistry are all moderate drug interactions and are (according to drug group): (1) antibiotics: azithromycin, clavulanate, doxycycline, erythromycin, levofloxacin; (2) antifungals: clotrimazole, fluconazole, itraconazole, ketoconazole; (3) non-steroidal anti-inflammatories (NAIDS): celecoxib diclofenac, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam. CONCLUSIONS: It is clinically necessary for oral health professionals to be aware of possible drug interactions that may occur between remdesivir and drugs commonly prescribed in dentistry in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus , Odontologia , Interações Medicamentosas , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico
8.
Folia Med (Plovdiv) ; 62(3): 592-596, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33009760

RESUMO

INTRODUCTION: Despite clinical trials, there are still no approved specific therapies or any vaccine against COVID-19. The only option available is using investigational drugs for compassionate use. The update of the existing regulation regarding compassionate use is to ensure the effective and sustainable development of health policies and technologies over the COVID-19 pandemic and beyond. AIM: The present short communication aimed to highlight the need for early and expanded access to investigational drugs for compassionate use as well as a call for an update of the existing regulation in Bulgaria concerning compassionate use in the era of COVID-19. MATERIALS AND METHODS: In EU and Bulgaria as well, the legal framework for compassionate use was introduced by Article 83 (1) of Regulation (EC) No 726/2004 of the European Parliament and of the Council; in principle, Regulations of the European Parliament and of the Council are mandatory for all Member States. Remdesivir appears to have a favorable clinical and safety profile, as reported in a case involving patients with severe COVID-19 through a compassionate use programme. RESULTS: The overall probability of clinical improvement observed in 36 of 53 COVID-19 patients received intravenous remdesivir as part of a compassionate use programme was 68% (95% CI 40% to 80%). Thirty two patients (60%) demonstrated at least one adverse event, twelve 12 patients (23%) experienced serious adverse events and seven patients (13%) died. CONCLUSION: The global pandemic mandates Bulgarian Drug Agency for a reasonable update of the existing national regulation concerning compassionate use and off-label therapies. In the era of COVID-19, it is important for Bulgarian patients to have early and expanded access to investigational drugs for compassionate use.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Ensaios de Uso Compassivo/legislação & jurisprudência , Infecções por Coronavirus/tratamento farmacológico , Política de Saúde/legislação & jurisprudência , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Betacoronavirus , Bulgária , Drogas em Investigação , Humanos , Pandemias
13.
Mol Genet Genomics ; 295(6): 1529-1535, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32894358

RESUMO

Lanthipeptides are a subgroup of ribosomally encoded and post-translationally modified peptides (RiPPs) which frequently possess potent biological activity. Here we provide the first comprehensive bioinformatic analysis of the lanthipeptide-producing capability of the Salinispora genus, a marine actinomycete. One hundred twenty-two Salinispora arenicola, tropica, and pacifica genomic sequences were analyzed for lanthipeptide gene clusters, and the resulting 182 clusters were divided into seven groups based on sequence similarities. Group boundaries were defined based on LanB and LanM sequences with greater than 80% similarity within groups. Of the seven groups, six are predicted to encode class I lanthipeptides while only one group is predicted to encode class II lanthipeptides. Leader and core peptides were predicted for each cluster along with the number of possible lanthionine bridges. Notably, all of the predicted products of these clusters would represent novel lanthipeptide scaffolds. Of the 122 Salinispora genomes analyzed in this study, 92% contained at least one lanthipeptide gene cluster suggesting that Salinispora is a rich, yet untapped, source of lanthipeptides.


Assuntos
Alanina/análogos & derivados , Proteínas de Bactérias/metabolismo , Genoma Bacteriano , Micromonosporaceae/metabolismo , Fragmentos de Peptídeos/metabolismo , Sulfetos/metabolismo , Alanina/isolamento & purificação , Alanina/metabolismo , Proteínas de Bactérias/genética , Genômica , Micromonosporaceae/genética , Micromonosporaceae/crescimento & desenvolvimento , Fragmentos de Peptídeos/isolamento & purificação , Sulfetos/isolamento & purificação
14.
Drugs ; 80(13): 1355-1363, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32870481

RESUMO

The antiviral agent remdesivir (Veklury®; Gilead Sciences), nucleotide analogue prodrug, has broad-spectrum activity against viruses from several families. Having demonstrated potent antiviral activity against coronaviruses in preclinical studies, remdesivir emerged as a candidate drug for the treatment of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during the current global pandemic. Phase III evaluation of remdesivir in the treatment of COVID-19 commenced in early 2020 and has thus far yielded promising results. In late May 2020, Taiwan conditionally approved the use of remdesivir in patients with severe COVID-19. This was followed by a rapid succession of conditional approvals in various countries/regions including the EU and Canada. Preceding these conditional approvals, an emergency use authorization for remdesivir had been granted in the USA (on 1 May 2020) and a special approval for emergency use was granted in Japan (on 7 May 2020). This article summarizes the milestones in the development of remdesivir leading to its first conditional approval for the treatment of COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus , Desenvolvimento de Medicamentos , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
17.
Eur Rev Med Pharmacol Sci ; 24(17): 9188-9195, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965013

RESUMO

OBJECTIVE: There have been significant changes to the management of COVID-19 in recent months, including protocols and guidelines designed to prevent, diagnose, and treat the Novel Coronavirus (COVID-19). Several management options have been suggested and have since gained popularity, though we expect additional modifications to be made, as well as more new cases in the coming months, given a lack of definitive treatment and well-controlled experiments. This review highlights the available and potential treatments, along with the challenges associated with each. MATERIALS AND METHODS: We conducted a comprehensive overview of all peer-reviewed studies, editorial comments, and letters to the editor based on a search in PubMed, Google Scholar, Web of Science, and Scopus. The following terms were used: "COVID-19," "SARS-CoV-2," "drug," "treatment," "medication," and "management." All searches were done between March and May 20, 2020. RESULTS: There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib. However, we do not have a definitive and specific treatment yet. CONCLUSIONS: We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus/isolamento & purificação , Cloroquina/análogos & derivados , Cloroquina/uso terapêutico , Infecções por Coronavirus/virologia , Humanos , Mesilato de Imatinib/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Pneumonia Viral/virologia , Ritonavir/uso terapêutico
18.
Eur Rev Med Pharmacol Sci ; 24(17): 9208-9215, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965016

RESUMO

OBJECTIVE: In December 2019, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection broke out in Wuhan, China. However, we still lack a comprehensive understanding of this emerging virus. In this manuscript, we collected relevant articles and reviewed the characteristics about SARS-CoV-2. MATERIALS AND METHODS: We performed an online search on PubMed and Web of Science with the keywords COVID-19, 2019-nCoV and SARS-CoV-2, and summarized the epidemiology, virology, clinical features and treatments of SARS-CoV-2 infection. RESULTS: We retrieved 157 published papers about SARS-CoV-2 from January, 2020 to April, 2020. We found that SARS-CoV-2 was a kind of virus with low mortality rate and high infectivity. This virus can enter human cells through angiotensin-converting enzyme 2 (ACE2) in alveoli and activate immune response in human body. SARS-CoV-2 infection can be classified as asymptomatic, mild, common, severe, and critical. We summarized antiviral drugs against SARS-CoV-2, such as remdesivir, hydroxychloroquine and favipiravir. Because the vaccine of SARS-CoV-2 is developing, more clinical studies are needed to verify the safety and efficacy of these treatments. CONCLUSIONS: SARS-CoV-2 is a novel coronavirus that has caused a global pandemic. We should pay more attention to prevent SARS-CoV-2 and try to control it sooner.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Oxigenação por Membrana Extracorpórea , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva , Imunoterapia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia
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