scholarly journals Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Junhyung Cho ◽  
Young Jae Lee ◽  
Je Hyoung Kim ◽  
Sang il Kim ◽  
Sung Soon Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Heart Diseases ◽  
Therapeutic Agents ◽  
Progeny Virus ◽  
Therapeutic Effects ◽  
Cardiac Diseases ◽  
Viral Inhibition ◽  
Nanomolar Concentration ◽  
Post Entry ◽  
Single Dose Treatment

Abstract 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.

scholarly journals Antiviral Activity of Digoxin and Ouabain against SARS-CoV-2 Infection and Its Implication for COVID-19

2020 ◽  
Author(s):  
Junhyung Cho ◽  
Young Jae Lee ◽  
Je-Hyoung Kim ◽  
Sang il Kim ◽  
Sung Soon Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Therapeutic Effect ◽  
Heart Diseases ◽  
Cardiac Injury ◽  
Drug Repurposing ◽  
Progeny Virus ◽  
Viral Inhibition ◽  
Virus Life Cycle ◽  
Post Entry ◽  
Single Dose Treatment

Abstract The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, among patients with COVID-19, 10–40% of those with cardiac injury have more comorbidities such as acute heart failure and lymphocytopenia. An efficient strategy to response this issue is drug repurposing with expecting antiviral activity and therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases and have antiviral activity against several coronaviruses. Thus, we aimed this study to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentration (IC50) of DIG, and OUA were determined at a nanomolar concentration. Progeny virus titers of single dose treatment of DIG and OUA were approximately 103 and 104-fold lower (> 99% inhibition) than that of non-treated control or chloroquine at 48 hour post-infection (hpi). Furthermore, therapeutic treatment of DIG and OUA inhibited over 99 % of SARS-CoV-2 replication, leading to viral inhibition at post entry stage of the virus life cycle. Collectively, these results suggested that DIG and OUA could be an alternative treatment for COVID-19 with potential therapeutic effect for patients with cardiovascular disease.

A Brief Introduction to Porphyrin Compounds Used in Tumor Imaging and Therapies

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Xiaoai Wu ◽  
Huawei Cai ◽  
Feng Qin ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Photoacoustic Imaging ◽  
Therapeutic Agents ◽  
Biochemical Properties ◽  
Therapeutic Effects ◽  
Future Prospects ◽  
Animal Tissues ◽  
Sonodynamic Therapy ◽  
Porphyrin Derivatives ◽  
Porphyrin Analogues

Abstract:: As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole subunits. Porphyrin analogues/derivatives possess multiple biochemical properties because of their unique structures and have been extensively investigated in cancer treatment. Studies have shown that porphyrins and their derivatives have the ability to locate in tumor cells in a variety of human cancers, and these compounds not only exhibit potent therapeutic effects as photodynamic agents but also show promising properties in medicinal imaging, such as MRI, photoacoustic imaging, fluorescence imaging and PET/SPECT imaging. This paper reviews the recent reports of porphyrin derivatives as therapeutic agents used in tumor therapies, such as sonodynamic therapy, photodynamic therapy and radiotherapy, as well as imaging agents for multimodality tumor imaging. The limitations of porphyrin-based compounds in tumor treatments and future prospects are also summarized.

scholarly journals Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 650
Author(s):  
Gunsup Lee ◽  
Shailesh Budhathoki ◽  
Geum-Young Lee ◽  
Kwang-ji Oh ◽  
Yeon Kyoung Ham ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antiviral Activity ◽  
Broad Spectrum ◽  
Recombinant Antibody ◽  
Therapeutic Effects ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Diarrhea Virus ◽  
3D8 Scfv

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

scholarly journals Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Chaker El Kalamouni ◽  
Etienne Frumence ◽  
Sandra Bos ◽  
Jonathan Turpin ◽  
Brice Nativel ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Heme Oxygenase ◽  
Zika Virus ◽  
Fluorescent Protein ◽  
Human Cells ◽  
Heme Oxygenase 1 ◽  
Viral Inhibition ◽  
Reporter Protein ◽  
Wide Range ◽  
Rna Replicon

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect.

scholarly journals The Cardioprotective Effects of Hydrogen Sulfide in Heart Diseases: From Molecular Mechanisms to Therapeutic Potential

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yaqi Shen ◽  
Zhuqing Shen ◽  
Shanshan Luo ◽  
Wei Guo ◽  
Yi Zhun Zhu
Keyword(s):  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Cardiac Diseases ◽  
Mammalian Tissues ◽  
Antioxidative Action

Hydrogen sulfide (H2S) is now recognized as a third gaseous mediator along with nitric oxide (NO) and carbon monoxide (CO), though it was originally considered as a malodorous and toxic gas. H2S is produced endogenously from cysteine by three enzymes in mammalian tissues. An increasing body of evidence suggests the involvement of H2S in different physiological and pathological processes. Recent studies have shown that H2S has the potential to protect the heart against myocardial infarction, arrhythmia, hypertrophy, fibrosis, ischemia-reperfusion injury, and heart failure. Some mechanisms, such as antioxidative action, preservation of mitochondrial function, reduction of apoptosis, anti-inflammatory responses, angiogenic actions, regulation of ion channel, and interaction with NO, could be responsible for the cardioprotective effect of H2S. Although several mechanisms have been identified, there is a need for further research to identify the specific molecular mechanism of cardioprotection in different cardiac diseases. Therefore, insight into the molecular mechanisms underlying H2S action in the heart may promote the understanding of pathophysiology of cardiac diseases and lead to new therapeutic targets based on modulation of H2S production.

scholarly journals Antibody-based antiangiogenic and antilymphangiogenic therapies to prevent tumor growth and progression.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Monika Bzowska ◽  
Renata Mężyk-Kopeć ◽  
Tomasz Próchnicki ◽  
Małgorzata Kulesza ◽  
Tomasz Klaus ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Lymphatic Vessels ◽  
Therapeutic Agents ◽  
Signaling Networks ◽  
Therapeutic Effects ◽  
Combined Treatments ◽  
Tumor Drug Resistance ◽  
Prevent Tumor Growth

Blood and lymphatic vessel formation is an indispensable factor for cancer progression and metastasis. Therefore, various strategies designed to block angiogenesis and lymphangiogenesis are being investigated in the hope to arrest and reverse tumor development. Monoclonal antibodies, owing to their unequalled diversity and specificity, might be applied to selectively inhibit the pathways that cancer cells utilize to build up a network of blood vessels and lymphatics. Among the possible targets of antibody-based therapies are proangiogenic and prolymphangiogenic growth factors from the VEGF family and the receptors to which they bind (VEGFRs). Here, we present molecular mechanisms of angiogenesis and lymphangiogenesis exploited by tumors to progress and metastasise, with examples of antibody-based therapeutic agents directed at interfering with these processes. The expanding knowledge of vascular biology helps to explain some of the problems encountered in such therapies, that arise due to the redundancy in signaling networks controlling the formation of blood and lymphatic vessels, and lead to tumor drug resistance. Nonetheless, combined treatments and treatments focused on newly discovered proangiogenic and prolymphangiogenic factors give hope that more prominent therapeutic effects might be achieved in the future.

Clinical analyses of 383 cases with maternal cardiac diseases

2018 ◽  
Vol 46 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Emine Aydin ◽  
Ozgur Ozyuncu ◽  
Dila Kasapoglu ◽  
Gokcen Orgul ◽  
Necla Ozer ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Heart Diseases ◽  
Class Ii ◽  
World Health ◽  
Main Concern ◽  
Cardiac Diseases ◽  
Class Iii ◽  
Mortality And Morbidity ◽  
Eisenmenger’S Syndrome ◽  
Health Organization

Abstract Aim: To evaluate the pregnancy outcomes of women with heart disease. Materials and methods: In this retrospective study, 383 pregnant women with cardiac diseases were examined. The cases were classified according to the World Health Organization (WHO) classification. The distribution of the cases according to class, congenital heart diseases, mean birthweight, mean gestational week at delivery, type of delivery [cesarean section (CS) or vaginal delivery], and cardivascular events (during pregnancy and puerperium) were evaluated. Results: Of the 383 patients, 25 were in Class I; 39, Class II; 255, Class II or III; 31, Class III; and 33, Class IV cardiac diseases. The neonatal birth weights were significantly lower in Class III than in Classes II, and II or III. The preterm delivery rate was higher in Class III than in the other classes. Delivery was performed by CS due to cardiac indications in the high-risk classes, however, only obstetric indications were considered in the low-risk classes. Only one case of maternal death occurred during the postpartum period, in a patient with Eisenmenger’s syndrome. Discussion: Cardiovascular diseases are an important cause of mortality and morbidity in pregnancy. The adverse impact of cardiovascular disorders on pregnancy outcomes should be the main concern during the management of these women.

Berberine on the Prevention and Management of Cardiometabolic Disease: Clinical Applications and Mechanisms of Action

2021 ◽  
pp. 1-22
Author(s):  
Richard Y. Cao ◽  
Yuntao Zheng ◽  
Ying Zhang ◽  
Lingling Jiang ◽  
Qing Li ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Biological Activities ◽  
Heart Diseases ◽  
Wide Spectrum ◽  
Adenosine Monophosphate ◽  
Ionic Channels ◽  
Cardiometabolic Disease ◽  
Therapeutic Effects ◽  
Ampk Signaling ◽  
Traditional Chinese Herbal Medicine

Berberine is an alkaloid from several medicinal plants originally used to treat diarrhea and dysentery as a traditional Chinese herbal medicine. In recent years, berberine has been discovered to exhibit a wide spectrum of biological activities in the treatment of diverse diseases ranging from cancer and neurological dysfunctions to metabolic disorders and heart diseases. This review article summarizes the clinical practice and laboratory exploration of berberine for the treatment of cardiometabolic and heart diseases, with a focus on the novel insights and recent advances of the underlying mechanisms recognized in the past decade. Berberine was found to display pleiotropic therapeutic effects against dyslipidemia, hyperglycemia, hypertension, arrhythmia, and heart failure. The mechanisms of berberine for the treatment of cardiometabolic disease involve combating inflammation and oxidative stress such as inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) activation, regulating electrical signals and ionic channels such as targeting human ether-a-go-go related gene (hERG) currents, promoting energy metabolism such as activating adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, modifying gut microbiota to promote transforming of berberine into its intestine-absorbable form, and interacting with non-coding RNAs via targeting multiple signaling pathways such as AMPK, mechanistic target of rapamycin (mTOR), etc. Collectively, berberine appears to be safe and well-tolerated in clinical practice, especially for those who are intolerant to statins. Knowledge from this field may pave the way for future development of more effective pharmaceutical approaches for managing cardiometabolic risk factors and preventing heart diseases.

scholarly journals A silkworm–baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines

2008 ◽  
Vol 89 (1) ◽  
pp. 188-194 ◽  
Author(s):  
Yutaka Orihara ◽  
Hiroshi Hamamoto ◽  
Hiroshi Kasuga ◽  
Toru Shimada ◽  
Yasushi Kawaguchi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Vero Cells ◽  
Infection Model ◽  
Nuclear Magnetic Resonance Analysis ◽  
Therapeutic Effects ◽  
Traditional Medicines ◽  
Baculovirus Infection ◽  
Simplex Virus

Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm–baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.

scholarly journals Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

2020 ◽  
Vol 21 (12) ◽  
pp. 4472
Author(s):  
Tamara Szabados ◽  
Kamilla Gömöri ◽  
Laura Pálvölgyi ◽  
Anikó Görbe ◽  
István Baczkó ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ion Channel ◽  
Transient Receptor Potential ◽  
Heart Diseases ◽  
Receptor Potential ◽  
Cell Types ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Cardiac Diseases ◽  
Trpv1 Channels

Cardiovascular diseases, including coronary artery disease, ischemic heart diseases such as acute myocardial infarction and postischemic heart failure, heart failure of other etiologies, and cardiac arrhythmias, belong to the leading causes of death. Activation of capsaicin-sensitive sensory nerves by the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor and other receptors, as well as neuropeptide mediators released from them upon stimulation, play important physiological regulatory roles. Capsaicin-sensitive sensory nerves also contribute to the development and progression of some cardiac diseases, as well as to mechanisms of endogenous stress adaptation leading to cardioprotection. In this review, we summarize the role of capsaicin-sensitive afferents and the TRPV1 ion channel in physiological and pathophysiological functions of the heart based mainly on experimental results and show their diagnostic or therapeutic potentials. Although the actions of several other channels or receptors expressed on cardiac sensory afferents and the effects of TRPV1 channel activation on different non-neural cell types in the heart are not precisely known, most data suggest that stimulation of the TRPV1-expressing sensory nerves or stimulation/overexpression of TRPV1 channels have beneficial effects in cardiac diseases.

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