scholarly journals Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials

Theranostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 1207-1231
Author(s):  
Young Joo Han ◽  
Keum Hwa Lee ◽  
Sojung Yoon ◽  
Seoung Wan Nam ◽  
Seohyun Ryu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Middle East Respiratory Syndrome

scholarly journals Anticancer Effects of Disulfiram: A Systematic Review of in Vitro, Animal, and Human Studies

2021 ◽  
Author(s):  
ling wang ◽  
yang yu ◽  
cong zhou ◽  
run wan ◽  
Yumin Li
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Animal Models ◽  
Human Studies ◽  
Cochrane Library ◽  
Future Research ◽  
Tumor Inhibition ◽  
Anti Tumor Activity

Abstract Background and objectives: Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Several preclinical and clinical studies have examined the potential of repurposing disulfiram (DSF) as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans.Methods: Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics.Results: Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule.Conclusions: This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.

scholarly journals Immunotherapeutic Efficacy of IgY Antibodies Targeting the Full-Length Spike Protein in an Animal Model of Middle East Respiratory Syndrome Coronavirus Infection

2021 ◽  
Vol 14 (6) ◽  
pp. 511
Author(s):  
Sherif A. El-Kafrawy ◽  
Aymn T. Abbas ◽  
Sayed S. Sohrab ◽  
Ashraf A. Tabll ◽  
Ahmed M. Hassan ◽  
...  
Keyword(s):  
Middle East ◽  
Specific Binding ◽  
High Titer ◽  
Egg Yolk ◽  
Middle East Respiratory Syndrome ◽  
Therapeutic Interventions ◽  
Dot Blot ◽  
S Protein

Identified in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often fatal acute respiratory illness in humans. No approved prophylactic or therapeutic interventions are currently available. In this study, we developed chicken egg yolk antibodies (IgY Abs) specific to the MERS-CoV spike (S) protein and evaluated their neutralizing efficiency against MERS-CoV infection. S-specific IgY Abs were produced by injecting chickens with the purified recombinant S protein of MERS-CoV at a high titer (4.4 mg/mL per egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated specific binding to the MERS-CoV S protein. In vitro neutralization of the generated IgY Abs against MERS-CoV was evaluated and showed a 50% neutralizing concentration of 51.42 μg/mL. In vivo testing using a human-transgenic mouse model showed a reduction of viral antigen positive cells in treated mice, compared to the adjuvant-only controls. Moreover, the lung cells of the treated mice showed significantly reduced inflammation, compared to the controls. Our results show efficient neutralization of MERS-CoV infection both in vitro and in vivo using S-specific IgY Abs. Clinical trials are needed to evaluate the efficiency of the IgY Abs in camels and humans.

scholarly journals In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

2021 ◽  
Vol Volume 14 ◽  
pp. 2121-2131
Author(s):  
Ayman Mubarak ◽  
Bahauddeen Alrfaei ◽  
Abdullah Aljurayyan ◽  
Mahfoudh M Alqafil ◽  
Mohamed A Farrag ◽  
...  
Keyword(s):  
Middle East ◽  
Expression Profiles ◽  
Cytokine Expression ◽  
Middle East Respiratory Syndrome ◽  
In Vitro Evaluation

scholarly journals Mildly Infected and Presumed Asymptomatic Carriers of SARS-CoV-2; Implications in Spread and Control of COVID-19

2020 ◽  
Vol 1 (supplement) ◽  
Author(s):  
Raees Khan ◽  
Shumaila Naz ◽  
Fawad Muhammad ◽  
Syed Babar Jamal ◽  
Sumra Wajid Abbasi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Middle East Respiratory Syndrome ◽  
Asymptomatic Carriers ◽  
Death Toll ◽  
The World ◽  
Asymptomatic Individuals ◽  
And Control ◽  
Active Investigation

The death toll and the total number of infected individuals due to the ongoing pandemic of SARS-CoV-2 infection have exceeded that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) as the disease has raged around the world. So far the global efforts to tackle COVID-19 include the launch of Sputnik V vaccine by Russia, 42 vaccines presently undergoing clinical trials on humans and around 92 vaccines under preclinical active investigation in animals. Majority of the SARS-CoV-2 infected individuals have been reported to show mild symptoms whereas a considerable number show no symptoms at all. SARS-CoV-2 is believed to spread from infected individuals who are asymptomatic in addition to the symptomatic individuals. In this review we discussed how the mildly infected and asymptomatic individuals raise serious concerns and complicate the processes of screening, detection, quarantine, tracking and treatmentthatareinpracticetopreventthetransmissionofthe COVID-19.

scholarly journals COVID-19: The Immune Responses and Clinical Therapy Candidates

2020 ◽  
Vol 21 (15) ◽  
pp. 5559 ◽  
Author(s):  
Sareh Zhand ◽  
Marie Saghaeian Jazi ◽  
Saeed Mohammadi ◽  
Roozbeh Tarighati Rasekhi ◽  
Ghassem Rostamian ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Middle East Respiratory Syndrome ◽  
Adults And Children ◽  
Repurposed Drugs ◽  
Present Understanding

The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2’s molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.

scholarly journals Curcumin as a Therapeutic Agent in Dementia: A Mini Systematic Review of Human Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Natascia Brondino ◽  
Simona Re ◽  
Annalisa Boldrini ◽  
Antonella Cuccomarino ◽  
Niccolò Lanati ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Therapeutic Agent ◽  
Short Term ◽  
Dementia Patients ◽  
Indian Medicine ◽  
Present Systematic Review ◽  
Potential Use

Dementia is a leading health problem worldwide, with Alzheimer’s disease (AD) representing up to 60% of all dementia cases. A growing interest has recently risen on the potential use of natural molecules in this condition. Curcumin is a polyphenolic compound traditionally used in Indian medicine. Severalin vitroandin vivostudies have found a protective effect of curcumin in AD. In the present systematic review we aimed to evaluate the state-of-the-art of clinical trials of curcumin in AD. We retrieved three published studies, while there are several ongoing clinical trials. To date there is insufficient evidence to suggest the use of curcumin in dementia patients. Of note, short-term use of curcumin appears to be safe. Several reasons could be responsible for the discrepancy betweenin vitroandin vivofindings and human trials, such as low bioavailability and poor study design.

scholarly journals Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus via interferon-λ in vitro and in mice

2020 ◽  
Vol 56 (5) ◽  
pp. 1901826 ◽  
Author(s):  
Lucie Sauerhering ◽  
Alexandra Kupke ◽  
Lars Meier ◽  
Erik Dietzel ◽  
Judith Hoppe ◽  
...  
Keyword(s):  
Middle East ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Middle East Respiratory Syndrome ◽  
Alveolar Epithelial Cells ◽  
Infection Model ◽  
Activated T Cells ◽  
Rna Accumulation

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome.We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.

scholarly journals Antiviral Activity of Ivermectin Against SARS-CoV-2: An Old-Fashioned Dog with a New Trick—A Literature Review

2020 ◽  
Vol 88 (3) ◽  
pp. 36 ◽  
Author(s):  
Mudatsir Mudatsir ◽  
Amanda Yufika ◽  
Firzan Nainu ◽  
Andri Frediansyah ◽  
Dewi Megawati ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Literature Review ◽  
Antiviral Activity ◽  
In Vivo Studies ◽  
Investigational Drug ◽  
Modeling Analysis ◽  
Global Threat

The coronavirus disease 2019 (COVID-19) pandemic is a major global threat. With no effective antiviral drugs, the repurposing of many currently available drugs has been considered. One such drug is ivermectin, an FDA-approved antiparasitic agent that has been shown to exhibit antiviral activity against a broad range of viruses. Recent studies have suggested that ivermectin inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus suggesting its potential for use against COVID-19. This review has summarized the evidence derived from docking and modeling analysis, in vitro and in vivo studies, and results from new investigational drug protocols, as well as clinical trials, if available, which will be effective in supporting the prospective use of ivermectin as an alternative treatment for COVID-19.

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