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1.
MMWR Morb Mortal Wkly Rep ; 69(47): 1782-1786, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33237895

RESUMO

To reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and its associated impacts on health and society, COVID-19 vaccines are essential. The U.S. government is working to produce and deliver safe and effective COVID-19 vaccines for the entire U.S. population. The Advisory Committee on Immunization Practices (ACIP)* has broadly outlined its approach for developing recommendations for the use of each COVID-19 vaccine authorized or approved by the Food and Drug Administration (FDA) for Emergency Use Authorization or licensure (1). ACIP's recommendation process includes an explicit and transparent evidence-based method for assessing a vaccine's safety and efficacy as well as consideration of other factors, including implementation (2). Because the initial supply of vaccine will likely be limited, ACIP will also recommend which groups should receive the earliest allocations of vaccine. The ACIP COVID-19 Vaccines Work Group and consultants with expertise in ethics and health equity considered external expert committee reports and published literature and deliberated the ethical issues associated with COVID-19 vaccine allocation decisions. The purpose of this report is to describe the four ethical principles that will assist ACIP in formulating recommendations for the allocation of COVID-19 vaccine while supply is limited, in addition to scientific data and implementation feasibility: 1) maximize benefits and minimize harms; 2) promote justice; 3) mitigate health inequities; and 4) promote transparency. These principles can also aid state, tribal, local, and territorial public health authorities as they develop vaccine implementation strategies within their own communities based on ACIP recommendations.


Assuntos
Infecções por Coronavirus/prevenção & controle , Alocação de Recursos para a Atenção à Saúde/ética , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/administração & dosagem , Comitês Consultivos , Centers for Disease Control and Prevention, U.S. , Infecções por Coronavirus/epidemiologia , Aprovação de Drogas/legislação & jurisprudência , Humanos , Imunização/normas , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
6.
J Mol Graph Model ; 101: 107758, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33007575

RESUMO

A novel strain of coronavirus, namely, SARS-CoV-2 identified in Wuhan city of China in December 2019, continues to spread at a rapid rate worldwide. There are no specific therapies available and investigations regarding the treatment of this disease are still lacking. In order to identify a novel potent inhibitor, we performed blind docking studies on the main virus protease Mpro with eight approved drugs belonging to four pharmacological classes such as: anti-malarial, anti-bacterial, anti-infective and anti-histamine. Among the eight studied compounds, Lymecycline and Mizolastine appear as potential inhibitors of this protease. When docked against Mpro crystal structure, these two compounds revealed a minimum binding energy of -8.87 and -8.71 kcal/mol with 168 and 256 binding modes detected in the binding substrate pocket, respectively. Further, to study the interaction mechanism and conformational dynamics of protein-ligand complexes, Molecular dynamic simulation and MM/PBSA binding free calculations were performed. Our results showed that both Lymecycline and Mizolastine bind in the active site. And exhibited good binding affinities towards target protein. Moreover, the ADMET analysis also indicated drug-likeness properties. Thus it is suggested that the identified compounds can inhibit Chymotrypsin-like protease (3CLpro) of SARS-CoV-2.


Assuntos
Cisteína Endopeptidases/química , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Animais , Antibacterianos/química , Antivirais/química , Antivirais/farmacocinética , Antivirais/farmacologia , Sítios de Ligação , Simulação por Computador , Cisteína Endopeptidases/metabolismo , Bases de Dados de Produtos Farmacêuticos , Aprovação de Drogas , Reposicionamento de Medicamentos , Antagonistas dos Receptores Histamínicos/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/farmacocinética , Proteínas não Estruturais Virais/metabolismo
7.
BioDrugs ; 34(6): 705-711, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33048300

RESUMO

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that was initially developed for various cancers and was later developed and approved in India for treatment of moderate to severe chronic plaque psoriasis in 2013. This drug is now being re-purposed for COVID-19. The potential utility of itolizumab in COVID-19, based on its unique mechanism of action in ameliorating cytokine release syndrome (CRS), was proposed first in Cuba with approval of a single-arm clinical trial and expanded access use. Subsequently, a phase II, open-label, randomized, placebo-controlled trial has been conducted in 30 COVID-19 patients in India after receiving regulatory permission. Based on the results, the Indian drug regulatory agency recently approved itolizumab in July 2020 for 'restricted emergency use' for the treatment of CRS in moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. This has drawn sharp criticism within the scientific community, with the approval being granted on the basis of a relatively small phase II trial, without conduct of a conventional phase III trial, and lacking availability of the claimed supportive real-world evidence in the public domain to date. In a global scenario where finding a successful treatment for COVID-19 is of utmost priority, a biologic agent has been re-purposed and approved with a successfully completed RCT, in a country where cases and mortality due to COVID-19 are growing exponentially. However, instead of welcoming the approval with open arms, many doubts are being raised. This is an issue that needs to be considered and dealt with sensitively, as well as scientifically.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Aprovação de Drogas , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Reposicionamento de Medicamentos , Humanos , Índia , Pandemias
9.
Colomb Med (Cali) ; 51(2): e4279, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33012890

RESUMO

Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. With the advance of COVID-19 and the pandemic declaration; It has become the closest alternative to reduce the advance of the virus. Antimalarial, antiviral drugs, antibiotics, glucocorticoids, monoclonal antibodies, among others, are being studied; their findings, although preliminary, could establish a starting point in the search for a solution. In this review, we present a selection of drugs, of different classes and with potential activity against COVID-19, whose trials are ongoing; and as proofs of concept, double blind, add-on event-driven, would allow proposing research that generates results in less time and preserving quality criteria for drug development and approval by regulatory agencies.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Aprovação de Drogas , Desenvolvimento de Medicamentos , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia
10.
BMJ ; 371: m3434, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028575

RESUMO

OBJECTIVE: To characterize the therapeutic value of new drugs approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) and the association between these ratings and regulatory approval through expedited programs. DESIGN: Retrospective cohort study. SETTING: New drugs approved by the FDA and EMA between 2007 and 2017, with follow-up through 1 April 2020. DATA SOURCES: Therapeutic value was measured using ratings of new drugs by five independent organizations (Prescrire and health authorities of Canada, France, Germany, and Italy). MAIN OUTCOME MEASURES: Proportion of new drugs rated as having high therapeutic value; association between high therapeutic value rating and expedited status. RESULTS: From 2007 through 2017, the FDA and EMA approved 320 and 268 new drugs, respectively, of which 181 (57%) and 39 (15%) qualified for least one expedited program. Among 267 new drugs with a therapeutic value rating, 84 (31%) were rated as having high therapeutic value by at least one organization. Compared with non-expedited drugs, a greater proportion of expedited drugs were rated as having high therapeutic value among both FDA approvals (45% (69/153) v 13% (15/114); P<0.001) and EMA approvals (67% (18/27) v 27% (65/240); P<0.001). The sensitivity and specificity of expedited program for a drug being independently rated as having high therapeutic value were 82% (95% confidence interval 72% to 90%) and 54% (47% to 62%), respectively, for the FDA, compared with 25.3% (16.4% to 36.0%) and 90.2% (85.0% to 94.1%) for the EMA. CONCLUSIONS: Less than a third of new drugs approved by the FDA and EMA over the past decade were rated as having high therapeutic value by at least one of five independent organizations. Although expedited drugs were more likely than non-expedited drugs to be highly rated, most expedited drugs approved by the FDA but not the EMA were rated as having low therapeutic value.


Assuntos
Aprovação de Drogas , Avaliação de Medicamentos , Serviços de Informação sobre Medicamentos , Disseminação de Informação , Vigilância de Produtos Comercializados , Aprovação de Drogas/métodos , Aprovação de Drogas/estatística & dados numéricos , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Serviços de Informação sobre Medicamentos/organização & administração , Serviços de Informação sobre Medicamentos/normas , Serviços de Informação sobre Medicamentos/estatística & dados numéricos , Europa (Continente) , Humanos , Vigilância de Produtos Comercializados/métodos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Desenvolvimento de Programas , Melhoria de Qualidade , Estudos Retrospectivos , Estados Unidos
13.
Expert Rev Clin Pharmacol ; 13(10): 1095-1101, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32909843

RESUMO

INTRODUCTION: There were no formal regulatory approvals for antivirals for the COVID-19 pandemic as of June 2020. AREAS COVERED: We compare the first regulatory approvals for remdesivir, through emergency pathways available to three of the main regulators in the world, the U.S., Japan, and the EU. We look at the data supporting the decisions and how authorities exchanged information and collaborated to speed up approvals. Based only on topline data available as of 29 April 2020, regulators granted approvals to remdesivir based on very limited but robust data and waiting for more safety and efficacy data. This included the Emergency Use Authorization in the U.S. on 1 May, the Special Approval for Emergency in Japan on 7 May, and Compassionate Use (3 April) followed by a Conditional Marketing Authorization in Europe (Opinion 25th June, Decision (3 July)). EXPERT OPINION: While the regulatory approvals were clearly based on evidence, regulators used agile methods to speed up approval, and make the first antiviral with reliable data available to patients in their constituencies in a very short time frame. More data and wider patient access are still necessary for this product, and more treatments are needed for patients affected by COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Aprovação de Drogas , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Betacoronavirus , Ensaios de Uso Compassivo , Serviços Médicos de Emergência , União Europeia , Humanos , Japão , Pandemias , Estados Unidos
14.
J Mol Graph Model ; 101: 107730, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920239

RESUMO

The SARS-CoV-2 main protease (Mpro) is an attractive target towards discovery of drugs to treat COVID-19 because of its key role in virus replication. The atomic structure of Mpro in complex with an α-ketoamide inhibitor (Lig13b) is available (PDB ID:6Y2G). Using 6Y2G and the prior knowledge that protease inhibitors could eradicate COVID-19, we designed a computational study aimed at identifying FDA-approved drugs that could interact with Mpro. We searched the DrugBank and PubChem for analogs and built a virtual library containing ∼33,000 conformers. Using high-throughput virtual screening and ligand docking, we identified Isavuconazonium, a ketoamide inhibitor (α-KI) and Pentagastrin as the top three molecules (Lig13b as the benchmark) based on docking energy. The ΔGbind of Lig13b, Isavuconazonium, α-KI, Pentagastrin was -28.1, -45.7, -44.7, -34.8 kcal/mol, respectively. Molecular dynamics simulation revealed that these ligands are stable within the Mpro active site. Binding of these ligands is driven by a variety of non-bonded interaction, including polar bonds, H-bonds, van der Waals and salt bridges. The overall conformational dynamics of the complexed-Mpro was slightly altered relative to apo-Mpro. This study demonstrates that three distinct classes molecules, Isavuconazonium (triazole), α-KI (ketoamide) and Pentagastrin (peptide) could serve as potential drugs to treat patients with COVID-19.


Assuntos
Cisteína Endopeptidases/química , Nitrilos/farmacologia , Pentagastrina/farmacologia , Inibidores de Proteases/farmacologia , Piridinas/farmacologia , Triazóis/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Antivirais/química , Antivirais/farmacologia , Domínio Catalítico , Simulação por Computador , Cisteína Endopeptidases/metabolismo , Bases de Dados de Produtos Farmacêuticos , Aprovação de Drogas , Descoberta de Drogas , Reposicionamento de Medicamentos , Ensaios de Triagem em Larga Escala/métodos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nitrilos/química , Pentagastrina/química , Inibidores de Proteases/química , Piridinas/química , Triazóis/química , Estados Unidos , United States Food and Drug Administration , Proteínas não Estruturais Virais/metabolismo
17.
Viruses ; 12(10)2020 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993136

RESUMO

In a short time, the COVID-19 pandemic has left the world with over 25 million cases and staggering death tolls that are still rising. Treatments for SARS-CoV-2 infection are desperately needed as there are currently no approved drug therapies. With limited knowledge of viral mechanisms, a network controllability method of prioritizing existing drugs for repurposing efforts is optimal for quickly moving through the drug approval pipeline using limited, available, virus-specific data. Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Of the 16, eight are prioritized as possible drug targets where two, PVR and SCARB1, are previously unexplored. Known compounds targeting these genes are suggested for viral inhibition study. Prioritized proteins in agreement with previous analysis and viral inhibition studies verify the ability of network controllability to predict biologically relevant candidates.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Aprovação de Drogas , Sistemas de Liberação de Medicamentos , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Receptores Virais/genética , Receptores Virais/metabolismo , Receptores Depuradores Classe B/metabolismo , Integração Viral
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