scholarly journals Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Bruno Silva Andrade ◽  
Fernanda de Souza Rangel ◽  
Naiane Oliveira Santos ◽  
Andria dos Santos Freitas ◽  
Wagner Rodrigues de Assis Soares ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Large Scale ◽  
Post Exposure Prophylaxis ◽  
Drug Candidates ◽  
Global Pandemic ◽  
The World ◽  
Approved Drugs ◽  
Exposure Prophylaxis

The SARS-CoV-2 outbreak originally appeared in China in December 2019 and became a global pandemic in March 2020. This infectious disease has directly affected public health and the world economy. Several palliative therapeutic treatments and prophylaxis strategies have been used to control the progress of this viral infection, including pre-(PrEP) and post-exposure prophylaxis. On the other hand, research groups around the world are still studying novel drug prophylaxis and treatment using repurposing approaches, as well as vaccination options, which are in different pre-clinical and clinical testing phases. This systematic review evaluated 1,228 articles from the PubMed and Scopus indexing databases, following the Kitchenham bibliographic searching protocol, with the aim to list drug candidates, potentially approved to be used as new options for SARS-CoV-2 prophylaxis clinical trials and medical protocols. In searching protocol, we used the following keywords: “Covid-19 or SARS-CoV-2” or “Coronavirus or 2019 nCoV,” “prophylaxis,” “prophylactic,” “pre-exposure,” “COVID-19 or SARS-CoV-2 Chemoprophylaxis,” “repurposed,” “strategies,” “clinical,” “trials,” “anti-SARS-CoV-2,” “anti-covid-19,” “Antiviral,” “Therapy prevention in vitro,” in cells “and” human testing. After all protocol steps, we selected 60 articles that included: 15 studies with clinical data, 22 studies that used in vitro experiments, seven studies using animal models, and 18 studies performed with in silico experiments. Additionally, we included more 22 compounds between FDA approved drugs and drug-like like molecules, which were tested in large-scale screenings, as well as those repurposed approved drugs with new mechanism of actions. The drugs selected in this review can assist clinical studies and medical guidelines on the rational repurposing of known antiviral drugs for COVID-19 prophylaxis.

scholarly journals The efficacy and safety of interferons for the treatment of patients with COVID-19: protocol for systematic review and meta-analysis of controlled trials

2021 ◽  
Author(s):  
Afsaneh Noormandi ◽  
Mohammad Fathalipour ◽  
Reza Daryabeygi-Khotbehsara ◽  
Soheil Hassanipour
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Meta Analysis ◽  
World Health ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Global Pandemic ◽  
The World ◽  
Health Organization ◽  
Time Of Administration

Background and objective: COVID-19 has since been declared a global pandemic by the World Health Organization (WHO), infecting millions worldwide. The use of Interferon (INF) subtypes previously examined in the treatment of SARS and MERS is also being initiated in some clinical trials. Although different clinical trials were evaluated IFNs in the treatment of COVID-19, their efficacy and safety remain unknown. Therefore, this study aims to systematically assess IFNs efficacy and safety in treating patients with COVID-19. Methods: The protocol has been registered in the PROSPERO International Prospective Register (CRD42020200643) on 24 July 2020. This protocol has been arranged according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 checklist. Discussion: Due to lack of approved medication for the covid-19 treatment and also various mutations of this virus, evaluated the efficacy and safety of medications by various studies could help for finding treatments with high effectiveness. IFNs are one of the medications that have been administered in covid-19 infection.  Moreover, the best time of administration and dose of this medication was unknown. Although meta-analysis is a potent source for assessing the accuracy of subjects, heterogeneity of articles is a potent limitation of our work.

scholarly journals Effectiveness Analysis of Single Dose Rifampicin-Post-Exposure Prophylaxis (SDR-PEP) as A Preventive Intervention for Leprosy Transmission: A Systematic Review of Randomized Controlled Trials

2021 ◽  
Vol 4 (2) ◽  
pp. 35-43
Author(s):  
Muhammad Mikail Athif Zhafir Asyura ◽  
Ilma Ranjani Wijaya ◽  
Theetouch Toshukowong ◽  
Rui Sheng Wang
Keyword(s):  
Systematic Review ◽  
Single Dose ◽  
Randomized Controlled Trials ◽  
Large Scale ◽  
Preventive Intervention ◽  
Post Exposure Prophylaxis ◽  
Controlled Trials ◽  
Post Exposure ◽  
Randomized Controlled ◽  
Exposure Prophylaxis

Introduction: Leprosy is a skin disease that reaches 200,000 cases annually. Considered a neglected tropical disease, 80% of annual leprosy remained in countries such as Brazil, India, and Indonesia. Multi-drug treatment is effective in curing leprosy but ineffective in preventing further transmission. The implementation of large-scale single dose rifampicin-post exposure prophylaxis suggests the inhibition of leprosy transmission and thus needs validation.Methods: This systematic review was carried out based on the PRISMA statement from multiple databases using set keywords. A total of 646 studies were identified, followed by 4 randomized controlled trials included after screening.Results: 86,502 subjects were divided into control and interventional groups and were to be followed up in 2-6 years. Most studies showed a significant decrease of leprosy cases by 50-60%. Furthermore, a complementary effect between single-dose rifampicin-post exposure prophylaxis and Bacillus Calmette–Guérin vaccine was identified. Moreover, the cost-effectiveness of the intervention was analyzed which resulted in IDR 80,414,775 being averted in its 25th year of implementationConclusion: The review established promising results of implementing single dose rifampicin-post exposure prophylaxis to prevent leprosy transmission. Further national scale intervention with a multi-layered approach is suggested to ensure full support and continuity of the large-scale intervention 

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

scholarly journals Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hu Zhu ◽  
Catherine Z. Chen ◽  
Srilatha Sakamuru ◽  
Jinghua Zhao ◽  
Deborah K. Ngan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Throughput Screening ◽  
Animal Studies ◽  
Cytopathic Effect ◽  
Mechanisms Of Action ◽  
Activity Profile ◽  
Pathway Activity ◽  
Global Pandemic ◽  
Approved Drugs

AbstractThe recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.

scholarly journals Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 438
Author(s):  
Jagadish Hosmani ◽  
Shazia Mushtaq ◽  
Shahabe Saquib Abullais ◽  
Hussain Mohammed Almubarak ◽  
Khalil Assiri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Oral Cancer ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Oral Leukoplakia ◽  
Research Articles ◽  
Original Research ◽  
Therapeutic Effects ◽  
The World

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

scholarly journals LICENSED ANTHRAX VACCINES AND EXPERIMENTAL PREPARATIONS AT THE STAGE OF CLINICAL TRIALS

2017 ◽  
pp. 112-126
Author(s):  
N. I. Mikshis ◽  
P. Yu. Popova ◽  
A. P. Semakova ◽  
V. V. Kutyrev
Keyword(s):  
Clinical Trials ◽  
Russian Federation ◽  
Large Scale ◽  
Next Generation ◽  
The World ◽  
High Pathogenicity ◽  
The Russian Federation ◽  
Manufacturing Technologies ◽  
Anthrax Vaccines ◽  
Epidemiological Situation

High pathogenicity of anthrax agent combined with unique insensitivity of its spore forms to environmental stresses class it among extremely dangerous biological agents. Registered and effectively used anthrax vaccines made invaluable contribution to the improvement of epidemiological situation around the world. Nevertheless, neglect of non-specific prophylaxis may result in dramatic scenarios and require large-scale measures on rectification of the consequences. Efforts on the development of next-generation vaccines are aimed at safety build-up, decrease in frequency of administration, and enhancement of manufacturing technologies. The review contains the key information on licensed anthrax vaccines designed for medical use, both in the territory of the Russian Federation and abroad. Among multiple experimental developments emphasized have been preparations manufactured by various biopharmaceutical companies in compliance with GMP standards, at different phases of clinical trials in 2016.

scholarly journals Recent update on COVID-19 in India: Is locking down the country enough?

2020 ◽  
Author(s):  
Jitender Singh Virk ◽  
Syed Azmal Ali ◽  
Gurjeet Kaur
Keyword(s):  
Growth Factor ◽  
Large Scale ◽  
Inflection Point ◽  
Indian Population ◽  
Lasso Regression ◽  
Logistic Curve ◽  
Global Pandemic ◽  
Care Facilities ◽  
The World ◽  
The Usa

AbstractBackgroundIndia is the second-largest population in the world, and it is not well equipped, hitherto, in the scenario of the global pandemic, SARS-CoV-2 could impart a devastating impact on the Indian population. Only way to respond against this critical condition is by practicing large-scale social distancing. India lock down for 21 days, however, till 7 April 2020, SARS- CoV-2 positive cases were growing exponentially, which raises the concerns if the number of reported and actual cases are similar.MethodsWe use Lasso Regression with α = 0.12 and Polynomial features of degree 2 to predict the growth factor. Also, we predicted Logistic curve using the Prophet Python. Further, using the growth rate to logistic, and carrying capacity is 20000 allowed us to calculate the maximum cases and new cases per day.ResultsWe found the predicted growth factor with a standard deviation of 0.3443 for the upcoming days. When the growth factor becomes 1.0, which is known as Inflection point, it will be safe to state that the rate is no longer exponential. The estimated time to reach the inflection point is between 15-20 April. At that time, the estimated number of total positive cases will be over 12500, if lockdown remains continue.ConclusionsOur analysis suggests that there is an urgent need to take action to extend the period of lockdown and allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. Otherwise, the outbreak in India can reach the level of the USA or Italy or could be worse than these countries within a few days or weeks, given the size of the population and lack of resources.

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