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1.
PLoS One ; 19(4): e0301086, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662719

RESUMO

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.


Assuntos
Antivirais , Iridoides , Simulação de Acoplamento Molecular , Olea , Extratos Vegetais , Folhas de Planta , Polifenóis , SARS-CoV-2 , Olea/química , Antivirais/farmacologia , Antivirais/química , SARS-CoV-2/efeitos dos fármacos , Folhas de Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Iridoides/farmacologia , Iridoides/química , Humanos , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/química , Glucosídeos/farmacologia , Glucosídeos/química , Metiltransferases/metabolismo , Metiltransferases/antagonistas & inibidores , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/química , Simulação por Computador , Tratamento Farmacológico da COVID-19 , Luteolina/farmacologia , Luteolina/química , RNA Helicases/metabolismo , RNA Helicases/antagonistas & inibidores , Apigenina/farmacologia , Apigenina/química
2.
J Pharm Biomed Anal ; 245: 116142, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631070

RESUMO

Traditional Chinese Medicine (TCM) is a supremely valuable resource for the development of drug discovery. Few methods are capable of hunting for potential molecule ligands from TCM towards more than one single protein target. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed to perform targeted compound screening of two key proteins involved in the cellular invasion process of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): the spike (S) protein receptor binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2). The screening and identification of active compounds from six Chinese herbs were conducted taking into consideration the multi-component and multi-target nature of Traditional Chinese Medicine (TCM). Puerarin from Radix Puerariae Lobatae was discovered to exhibit specific binding affinity to both S protein RBD and ACE2. The results highlight the efficiency of the dual-target SPR system in drug screening and provide a novel approach for exploring the targeted mechanisms of active components from Chinese herbs for disease treatment.


Assuntos
Enzima de Conversão de Angiotensina 2 , Medicamentos de Ervas Chinesas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Ressonância de Plasmônio de Superfície , Enzima de Conversão de Angiotensina 2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ligantes , Humanos , SARS-CoV-2/efeitos dos fármacos , Ligação Proteica , Medicina Tradicional Chinesa/métodos , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , COVID-19/virologia , Tratamento Farmacológico da COVID-19
3.
J Nat Med ; 78(3): 784-791, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512650

RESUMO

Papain-like protease (PLpro) enzyme plays a vital role in viral replication as it breaks down polyproteins and disrupts the host's immune response. There are few reports on Kampo formulas that focus on PLpro activity. In this study, we evaluated the inhibitory effects of senkyuchachosan, a traditional Japanese medicine, on PLpro of SARS-CoV-2, the virus responsible for causing COVID-19. We purified the PLpro enzyme and conducted in vitro enzymatic assays using specific substrates. Among the nine crude drugs present in senkyuchachosan, four (Cyperi Rhizoma, Schizonepetae Spica, Menthae Herba, and Camelliae sinensis Folium [CsF]) strongly inhibited PLpro activity. CsF, derived from Camellia sinensis (green tea), contains polyphenols, including catechins and tannins. To confirm that the PLpro inhibitory effects of senkyuchachosan predominantly stem from tannins, the tannins were removed from the decoction using polyvinylpolypyrrolidone (PVPP). The inhibitory effect of senkyuchachosan on PLpro activity was reduced by the removal of PVPP. In addition, the tannin fraction obtained from the CsF extracts showed significant PLpro inhibitory effects. These findings lay the groundwork for the potential development of therapeutic agents that target SARS-CoV-2 infection by intervening in proteolytic cleavage of the virus.


Assuntos
SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Humanos , Antivirais/farmacologia , Antivirais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Taninos/farmacologia , Medicina Kampo
4.
Virus Res ; 344: 199365, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38527669

RESUMO

Reading the viral genome through whole genome sequencing (WGS) enables the detection of changes in the viral genome. The rapid changes in the SARS-CoV-2 viral genome may cause immune escape leading to an increase in the pathogenicity or infectivity. Monitoring mutations through genomic surveillance helps understand the amino acid changes resulting from the mutation. These amino acid changes, especially in the spike glycoprotein, may have implications on the pathogenicity of the virus by rendering it immune-escape. The region of Vidarbha in Maharashtra represents 31.6 % of the state's total area. It holds 21.3 % of the total population. In total, 7457 SARS-CoV-2 positive samples belonging to 16 Indian States were included in the study, out of which 3002 samples passed the sequencing quality control criteria. The metadata of 7457 SARS-CoV-2 positive samples included in the study was sourced from the Integrated Health Information Platform (IHIP). The metadata of 3002 sequenced samples, including the FASTA sequence, was submitted to the Global Initiative on Sharing Avian Influenza Data (GISAID) and the Indian biological data centre (IBDC). This study identified 104 different SARS-CoV-2 pango-lineages classified into 19 clades. We have also analysed the mutation profiles of the variants found in the study, which showed eight mutations of interest, including L18F, K417N, K417T, L452R, S477N, N501Y, P681H, P681R, and mutation of concern E484K in the spike glycoprotein region. The study was from November 2020 to December 2022, making this study the most comprehensive genomic surveillance of SARS-CoV-2 conducted for the region.


Assuntos
COVID-19 , Genoma Viral , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Sequenciamento Completo do Genoma , Índia/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , COVID-19/epidemiologia , Humanos , Glicoproteína da Espícula de Coronavírus/genética , Filogenia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Adolescente , Criança
5.
J Biochem Mol Toxicol ; 37(5): e23320, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36799127

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 is a censorious global emergency after World War II. Research on the coronavirus uncovered essential information that aided in the development of the vaccine, and specific coronavirus disease 2019 (COVID-19) vaccines were later developed and were approved for usage in humans. But then, mutations in the coronavirus gave rise to new variants and questioned the vaccine's efficacy against them. On the other hand, the investigation of traditional medicine was also on its path to find a novel outcome against COVID-19. On a comparative analysis between India and the United States, India had low death rate and high recovery rate than the latter. The dietary regulation of immunity may be the factor that makes the above difference. The immunity gained from the regular diet of Indian culture nourishes Indian people with essential phytochemicals that support immunity and metabolism. Dietary phytochemicals or nutraceuticals possess antioxidant, anti-inflammatory, and anticancer properties, out of which our concern will be on immune-boosting phytochemicals from our daily nutritional supplements. In several case studies, dietary substance like lemon, ginger, and spinach was reported in the recovery of COVID-19 patients. Thus in this review, we discuss coronavirus and its available variants, vaccines, and the effect of nutraceuticals against the coronavirus. Further, we denote that the immunity of the Indian population may be high because of their diet, which adds natural phytochemicals to boost their immunity and metabolism.


Assuntos
COVID-19 , Suplementos Nutricionais , Imunomodulação , Humanos , COVID-19/dietoterapia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Curcumina , Alho , Zingiber officinale , Índia/epidemiologia , Moringa , Cebolas , Pandemias/prevenção & controle , Compostos Fitoquímicos/uso terapêutico , Piper nigrum , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Syzygium
6.
Biochem Biophys Res Commun ; 616: 8-13, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35636257

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a pandemic of acute respiratory disease, namely coronavirus disease 2019 (COVID-19). Currently, effective drugs for this disease are urgently warranted. Anisodamine is a traditional Chinese medicine that is predicted as a potential therapeutic drug for the treatment of COVID-19. Therefore, this study aimed to investigate its antiviral activity and crucial targets in SARS-CoV-2 infection. SARS-CoV-2 and anisodamine were co-cultured in Vero E6 cells, and the antiviral activity of anisodamine was assessed by immunofluorescence assay. The antiviral activity of anisodamine was further measured by pseudovirus entry assay in HEK293/hACE2 cells. Finally, the predictions of crucial targets of anisodamine on SARS-CoV-2 were analyzed by molecular docking studies. We discovered that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells, and reduced the SARS-CoV-2 pseudovirus entry to HEK293/hACE2 cells. Furthermore, molecular docking studies indicated that anisodamine may target SARS-CoV-2 main protease (Mpro) with the docking score of -6.63 kcal/mol and formed three H-bonds with Gly143, Cys145, and Cys44 amino acid residues at the predicted active site of Mpro. This study suggests that anisodamine is a potent antiviral agent for treating COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Proteases 3C de Coronavírus , SARS-CoV-2 , Alcaloides de Solanáceas , Antivirais/química , Antivirais/farmacologia , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/efeitos dos fármacos , Proteases 3C de Coronavírus/metabolismo , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Inibidores de Proteases/farmacologia , Alcaloides de Solanáceas/farmacologia , Proteínas não Estruturais Virais/química
7.
Molecules ; 27(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35268642

RESUMO

Diseases caused by viruses are a global threat, resulting in serious medical and social problems for humanity. They are the main contributors to many minor and major outbreaks, epidemics, and pandemics worldwide. Over the years, medicinal plants have been used as a complementary treatment in a range of diseases. In this sense, this review addresses promising antiviral plants from Marajó island, a part of the Amazon region, which is known to present a very wide biodiversity of medicinal plants. The present review has been limited to articles and abstracts available in Scopus, Web of Science, Science Direct, Scielo, PubMed, and Google Scholar, as well as the patent offices in Brazil (INPI), United States (USPTO), Europe (EPO) and World Intellectual Property Organization (WIPO). As a result, some plants from Marajó island were reported to have actions against HIV-1,2, HSV-1,2, SARS-CoV-2, HAV and HBV, Poliovirus, and influenza. Our major conclusion is that plants of the Marajó region show promising perspectives regarding pharmacological potential in combatting future viral diseases.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Extratos Vegetais/química , Plantas Medicinais/química , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Brasil , COVID-19/virologia , HIV-1/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação
8.
Molecules ; 27(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35268738

RESUMO

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).


Assuntos
Artemisia , Proteases 3C de Coronavírus , Flavonoides , SARS-CoV-2 , Animais , Humanos , Masculino , Ratos , Artemisia/química , Artemisia/metabolismo , Sítios de Ligação , Domínio Catalítico , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , COVID-19/patologia , COVID-19/virologia , Teoria da Densidade Funcional , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/metabolismo , Flavonoides/farmacologia , Dose Letal Mediana , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2/enzimologia , SARS-CoV-2/isolamento & purificação , Pele/efeitos dos fármacos , Pele/patologia
9.
Molecules ; 27(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35268843

RESUMO

The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities. We used pseudotyped HIV-1 with the D614G SARS-CoV-2 spike glycoprotein to test its ability to infect ACE2-expressing HEK 293T cells in the presence of diverse natural products, including 21 plant extracts, 7 essential oils, and 13 compounds from plants and fungi. The 50% cytotoxic concentration (CC50) was evaluated using the resazurin method. From these analyses, we determined the inhibitory activity of the extract of Stachytarpheta cayennensis, which had a half-maximal inhibitory concentration (IC50) of 91.65 µg/mL, a CC50 of 693.5 µg/mL, and a selectivity index (SI) of 7.57, indicating its potential use as an inhibitor of SARS-CoV-2 entry. Moreover, our work indicates the usefulness of the pseudotyped-virus system in the screening of SARS-CoV-2 entry inhibitors.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/química , Internalização do Vírus/efeitos dos fármacos , Actinobacteria/química , Actinobacteria/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/metabolismo , Antivirais/uso terapêutico , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , COVID-19/virologia , Células HEK293 , Ensaios de Triagem em Larga Escala/métodos , Humanos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/metabolismo , Tratamento Farmacológico da COVID-19
10.
Carbohydr Polym ; 285: 118971, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35287839

RESUMO

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.


Assuntos
Tratamento Farmacológico da COVID-19 , Ligusticum/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/virologia , Configuração de Carboidratos , Sequência de Carboidratos , Medicamentos de Ervas Chinesas , Humanos , Polissacarídeos/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação
11.
Int J Mol Sci ; 23(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35328419

RESUMO

The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Micronutrientes/metabolismo , Vitamina A/metabolismo , Vitamina D/metabolismo , Zinco/metabolismo , Animais , COVID-19/epidemiologia , COVID-19/metabolismo , COVID-19/virologia , Humanos , Micronutrientes/farmacologia , Pandemias/prevenção & controle , SARS-CoV-2/fisiologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Vitamina A/farmacologia , Vitamina D/farmacologia , Vitaminas/metabolismo , Vitaminas/farmacologia , Zinco/farmacologia
12.
Int J Mol Sci ; 23(6)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35328682

RESUMO

The recent covid crisis has provided important lessons for academia and industry regarding digital reorganization. Among the fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and beyond. Drug development is a costly and time-consuming business, and only a minority of approved drugs generate returns exceeding the research and development costs. As a result, there is a huge drive to make drug discovery cheaper and faster. With modern algorithms and hardware, it is not too surprising that the new technologies of artificial intelligence and other computational simulation tools can help drug developers. In only two years of covid research, many novel molecules have been designed/identified using artificial intelligence methods with astonishing results in terms of time and effectiveness. This paper reviews the most significant research on artificial intelligence in de novo drug design for COVID-19 pharmaceutical research.


Assuntos
Antivirais/química , Antivirais/farmacologia , Inteligência Artificial , Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Desenho de Fármacos , SARS-CoV-2/efeitos dos fármacos , Antivirais/uso terapêutico , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Ligantes , SARS-CoV-2/fisiologia , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade
13.
Horm Metab Res ; 54(3): 153-161, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35276740

RESUMO

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.


Assuntos
Hormônio Adrenocorticotrópico/sangue , COVID-19/imunologia , Hipotálamo/imunologia , Hipófise/imunologia , Adulto , Autoanticorpos/sangue , Autoimunidade , COVID-19/sangue , COVID-19/metabolismo , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/sangue , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Prolactina/sangue , Estudos Prospectivos , SARS-CoV-2/fisiologia , Testosterona/sangue
14.
Int J Mol Sci ; 23(5)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35269938

RESUMO

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.


Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Enoxaparina/farmacologia , Furina/antagonistas & inibidores , Espermina/análogos & derivados , Zeaxantinas/farmacologia , Clorometilcetonas de Aminoácidos/química , Clorometilcetonas de Aminoácidos/metabolismo , COVID-19/transmissão , COVID-19/virologia , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enoxaparina/química , Enoxaparina/metabolismo , Furina/química , Furina/metabolismo , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Proteólise , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Espermina/química , Espermina/metabolismo , Espermina/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Replicação Viral , Zeaxantinas/química , Zeaxantinas/metabolismo
15.
Int J Mol Sci ; 23(5)2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35270015

RESUMO

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.


Assuntos
COVID-19/imunologia , Diabetes Mellitus/imunologia , Sistema Imunitário/imunologia , Inflamação/imunologia , Obesidade/imunologia , Vitamina D/imunologia , COVID-19/virologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Metanálise como Assunto , SARS-CoV-2/fisiologia , Revisões Sistemáticas como Assunto , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Vitaminas/imunologia
16.
Pharm Biol ; 60(1): 509-524, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35234563

RESUMO

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Tratamento Farmacológico da COVID-19 , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Produtos Biológicos/isolamento & purificação , COVID-19/virologia , Desenvolvimento de Medicamentos/métodos , Sinergismo Farmacológico , Humanos , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia
17.
Nat Immunol ; 23(3): 360-370, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35210622

RESUMO

Host genetic and environmental factors including age, biological sex, diet, geographical location, microbiome composition and metabolites converge to influence innate and adaptive immune responses to vaccines. Failure to understand and account for these factors when investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy may impair the development of the next generation of vaccines. Most studies aimed at identifying mechanisms of vaccine-mediated immune protection have focused on adaptive immune responses. It is well established, however, that mobilization of the innate immune response is essential to the development of effective cellular and humoral immunity. A comprehensive understanding of the innate immune response and environmental factors that contribute to the development of broad and durable cellular and humoral immune responses to SARS-CoV-2 and other vaccines requires a holistic and unbiased approach. Along with optimization of the immunogen and vectors, the development of adjuvants based on our evolving understanding of how the innate immune system shapes vaccine responses will be essential. Defining the innate immune mechanisms underlying the establishment of long-lived plasma cells and memory T cells could lead to a universal vaccine for coronaviruses, a key biomedical priority.


Assuntos
Variação Biológica da População , Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Interações Hospedeiro-Patógeno/imunologia , Imunidade , SARS-CoV-2/imunologia , Anticorpos Antivirais , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Saúde Global , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Humoral , Imunidade Inata , Imunogenicidade da Vacina , Memória Imunológica , Microbiota/imunologia , Pandemias , Vigilância em Saúde Pública , Vacinação
18.
Bioengineered ; 13(3): 5480-5508, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35184680

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , Plantas Medicinais/química , SARS-CoV-2/efeitos dos fármacos , Antivirais/isolamento & purificação , COVID-19/patologia , COVID-19/virologia , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicina Herbária/métodos , Humanos , Medicina Tradicional Chinesa/métodos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade
19.
Eur Rev Med Pharmacol Sci ; 26(2): 715-721, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35113447

RESUMO

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.


Assuntos
Acetilcisteína/uso terapêutico , Tratamento Farmacológico da COVID-19 , Acetilcisteína/química , Antioxidantes/química , COVID-19/metabolismo , COVID-19/virologia , Glutationa/química , Glutationa/metabolismo , Humanos , Estresse Oxidativo , Ensaios Clínicos Controlados Aleatórios como Assunto , Espécies Reativas de Oxigênio/metabolismo , SARS-CoV-2/isolamento & purificação , Viroses/tratamento farmacológico , Viroses/metabolismo
20.
PLoS One ; 17(2): e0263937, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176073

RESUMO

The Covid-19 pandemic has negatively affected every aspect of human life. In these challenging times nursing students, facing academic and psychological issues, are advised to use augmented reality applications in the field of health sciences for increasing their motivations and academic performances. The main motive of the study was to examine the acceptance status of nursing students in implementing augmented reality technology in their education and training. The study is a quantitative research study, and it uses the causal-comparative screening method. The data used in the study was collected online from 419 nursing students. The hybrid method was preferred. First, the hypotheses based on the linear relationships were defined between the variables which were then tested by the method of structural equation modeling. Second, the method of artificial neural networks was used to determine the non-linear relationships between the variables. The results show that the nursing students have a high intention of using augmented reality technology as a way of self-learning. It was also found that the most emphasized motive behind this intention is the expectation that using augmented reality technology will increase their academic performance. They also think that AR technology has many potential benefits to offer in the future. It was observed that a considerable number of students already use augmented reality technology for its usefulness and with a hedonic motivation. In conclusion, nursing students have a high acceptance of using augmented reality technology during their education and training process. Since we live in a world where e-learning and self-learning education/training have become widespread, it is estimated that students will demand augmented reality applications as a part of holistic education, and as an alternative to traditional textbooks.


Assuntos
Desempenho Acadêmico/estatística & dados numéricos , Realidade Aumentada , COVID-19/psicologia , Educação em Enfermagem/normas , Aprendizagem , Motivação , Estudantes de Enfermagem/psicologia , Adulto , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Humanos , Intenção , Masculino , SARS-CoV-2/isolamento & purificação , Adulto Jovem
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