scholarly journals An Integrative Resource for Network-Based Investigation of COVID-19 Combinatorial Drug Repositioning and Mechanism of Action

2020 ◽  
Author(s):  
AKM Azad ◽  
Shadma Fatima ◽  
Fatemeh Vafaee
Keyword(s):  
Combination Therapy ◽  
Mechanism Of Action ◽  
Drug Repositioning ◽  
Clinical Investigation ◽  
Cost Effective ◽  
Similarity Score ◽  
Drug Combinations ◽  
Huge Number ◽  
Web Based ◽  
Therapeutic Development

<p>Repurposing of the existing medications has become the mainstream focus of anti-COVID-19 drug discovery as it offers rapid and cost-effective solutions for therapeutic development. However, there is still a great deal to enhance efficacy of repurposing therapeutic options through combination therapy, in which promising drugs with varying mechanisms of action are administered together. Nonetheless, our ability to identify and validate effective combinations is limited due to the huge number of possible drug pairs. Yet, there is no available resource which can systematically guide to identify or choose the effective individual drugs or best possible synergistic drug combinations for the treatment of SARS-CoV-2 infection. To address this resource gap, we developed a web-based platform that displays the network-based mechanism of action of drug combinations, thus simultaneously giving a visual of the cellular interactome involved in the mode of action of the chosen drugs. The platform allows the freedom to choose two or more drug combinations and provides the options to investigate network-based efficacy of drug combinations and understand the similarity score, primary indications, and contraindications of using these drugs combinations. In a nutshell, the platform (accessible via: <a href="http://vafaeelab.com/COVID19_repositioning.html">http://vafaeelab.com/COVID19_repositioning.html</a>) is of the first of its type which provides a systematic approach for pre-clinical investigation of combination therapy for treating COVID-19 on the fingertips of the clinicians or researchers.</p>

scholarly journals An Integrative Resource for Network-Based Investigation of COVID-19 Combinatorial Drug Repositioning and Mechanism of Action

2020 ◽  
Author(s):  
AKM Azad ◽  
Shadma Fatima ◽  
Fatemeh Vafaee
Keyword(s):  
Combination Therapy ◽  
Mechanism Of Action ◽  
Drug Repositioning ◽  
Clinical Investigation ◽  
Cost Effective ◽  
Similarity Score ◽  
Drug Combinations ◽  
Huge Number ◽  
Web Based ◽  
Therapeutic Development

<p>Repurposing of the existing medications has become the mainstream focus of anti-COVID-19 drug discovery as it offers rapid and cost-effective solutions for therapeutic development. However, there is still a great deal to enhance efficacy of repurposing therapeutic options through combination therapy, in which promising drugs with varying mechanisms of action are administered together. Nonetheless, our ability to identify and validate effective combinations is limited due to the huge number of possible drug pairs. Yet, there is no available resource which can systematically guide to identify or choose the effective individual drugs or best possible synergistic drug combinations for the treatment of SARS-CoV-2 infection. To address this resource gap, we developed a web-based platform that displays the network-based mechanism of action of drug combinations, thus simultaneously giving a visual of the cellular interactome involved in the mode of action of the chosen drugs. The platform allows the freedom to choose two or more drug combinations and provides the options to investigate network-based efficacy of drug combinations and understand the similarity score, primary indications, and contraindications of using these drugs combinations. In a nutshell, the platform (accessible via: <a href="http://vafaeelab.com/COVID19_repositioning.html">http://vafaeelab.com/COVID19_repositioning.html</a>) is of the first of its type which provides a systematic approach for pre-clinical investigation of combination therapy for treating COVID-19 on the fingertips of the clinicians or researchers.</p>

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

scholarly journals Integrative resource for network-based investigation of COVID-19 combinatoric drug repositioning and mechanism of action

Patterns ◽  
2021 ◽  
pp. 100325
Author(s):  
A.K.M. Azad ◽  
Shadma Fatima ◽  
Alexander Capraro ◽  
Shafagh A. Waters ◽  
Fatemeh Vafaee
Keyword(s):  
Mechanism Of Action ◽  
Drug Repositioning

scholarly journals Cost-effectiveness of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients with metastatic colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kiyoaki Sugiura ◽  
Yuki Seo ◽  
Takayuki Takahashi ◽  
Hideyuki Tokura ◽  
Yasuhiro Ito ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Health Care ◽  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Combination Therapy ◽  
Metastatic Colorectal Cancer ◽  
Cost Effective ◽  
Model Parameters ◽  
Combination Regimen ◽  
The Cost

Abstract Background TAS-102 plus bevacizumab is an anticipated combination regimen for patients who have metastatic colorectal cancer. However, evidence supporting its use for this indication is limited. We compared the cost-effectiveness of TAS-102 plus bevacizumab combination therapy with TAS-102 monotherapy for patients with chemorefractory metastatic colorectal cancer. Method Markov decision modeling using treatment costs, disease-free survival, and overall survival was performed to examine the cost-effectiveness of TAS-102 plus bevacizumab combination therapy and TAS-102 monotherapy. The Japanese health care payer’s perspective was adopted. The outcomes were modeled on the basis of published literature. The incremental cost-effectiveness ratio (ICER) between the two treatment regimens was the primary outcome. Sensitivity analysis was performed and the effect of uncertainty on the model parameters were investigated. Results TAS-102 plus bevacizumab had an ICER of $21,534 per quality-adjusted life-year (QALY) gained compared with TAS-102 monotherapy. Sensitivity analysis demonstrated that TAS-102 monotherapy was more cost-effective than TAS-102 and bevacizumab combination therapy at a willingness-to-pay of under $50,000 per QALY gained. Conclusions TAS-102 and bevacizumab combination therapy is a cost-effective option for patients who have metastatic colorectal cancer in the Japanese health care system.

scholarly journals Drug combination therapy increases successful drug repositioning

2016 ◽  
Vol 21 (7) ◽  
pp. 1189-1195 ◽  
Author(s):  
Wei Sun ◽  
Philip E. Sanderson ◽  
Wei Zheng
Keyword(s):  
Combination Therapy ◽  
Drug Combination ◽  
Drug Repositioning ◽  
Drug Combination Therapy

scholarly journals Why and How to Treat Chronic Hepatitis C

2000 ◽  
Vol 14 (suppl b) ◽  
pp. 45B-48B ◽  
Author(s):  
Stephanos J Hadziyannis
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Chronic Hepatitis C ◽  
Cost Effective ◽  
Genotype 1 ◽  
Related Factors ◽  
Major Health Problem ◽  
Hcv Genotype ◽  
End Stage

Chronic hepatitis C (CHC) is a major health problem worldwide, with approximately 200 million affected individuals and a significant rate of progression to end-stage cirrhosis and hepatocellular carcinoma (HCC). If hepatitis C virus (HCV) infection is left untreated in the population, then the number of liver-related deaths will soon double and the need for liver transplantation may increase to five times that seen today. Available therapies for CHC are restricted to interferon alpha (IFN-α ) monotherapy and to the combination of IFN-α and ribavirin. Despite their high cost and side effects, both of these therapies have proved to be cost effective, particularly combination therapy. IFN-α monotherapy for one year can induce sustained response (SR) rates of approximately 10% in naive patients infected with HCV genotype 1, and above 50% in those infected with other genotypes. Combination therapy can double or even triple the rate of SR in genotype 1 infections and may further increase the SR rate in the other HCV genotypes. Combination therapy has also been proven to be effective in approximately 50% of relapsed responders to IFN-α monotherapy. In clinical practice, the decision to treat should be individualized and tailored on the basis of several virus- and host-related factors, particularly the grade and stage of liver disease, HCV genotype and levels of viremia. Appropriate monitoring of therapy by careful clinical evaluation, liver biochemistry and serumHCVRNAtesting is mandatory. IFN-α therapy may also prove to be effective in reducing the rate of HCC development in CHC regardless of whether a virological response is achieved, but this remains to be established.

scholarly journals Treatment options in moderate and severe depression: decision analysis supporting a clinical guideline

2006 ◽  
Vol 189 (6) ◽  
pp. 494-501 ◽  
Author(s):  
Judit Simon ◽  
Stephen Pilling ◽  
Rachel Burbeck ◽  
David Goldberg
Keyword(s):  
Combination Therapy ◽  
Decision Analysis ◽  
Secondary Care ◽  
Treatment Options ◽  
Severe Depression ◽  
Cost Effective ◽  
Current Evidence ◽  
Resource Utilisation ◽  
Moderate Depression ◽  
The Cost

BackgroundTreatment options for depression include antidepressants, psychological therapy and a combination of the two.AimsTo develop cost-effective clinical guidelines.MethodSystematic literature reviews were used to identify clinical, utility and cost data. A decision analysis was then conducted to compare the benefits and costs of antidepressants with combination therapy for moderate and severe depression in secondary care in the UK.ResultsOver the 15-month analysis period, combination therapy resulted in higher costs and an expected 0.16 increase per person in the probability of remission and no relapse compared with antidepressants. The cost per additional successfully treated patient was £4056 (95% CI 1400–18 300); the cost per quality-adjusted life year gained was £5777 (95% CI 1900–33 800) for severe depression and £14 540 (95% CI 4800–79 400) for moderate depression.ConclusionsCombination therapy is likely to be a cost-effective first-line secondary care treatment for severe depression. Its cost-effectiveness for moderate depression is more uncertain from current evidence. Targeted combination therapy could improve resource utilisation.

A Web-Based Process/Material Advisory System

2000 ◽  
Author(s):  
Yusheng Chen ◽  
Satyandra K. Gupta ◽  
Shaw Feng
Keyword(s):  
Conceptual Design ◽  
Cost Effective ◽  
Design Stage ◽  
Material Combination ◽  
Web Based ◽  
Advisory System ◽  
Conceptual Design Stage ◽  
Design Requirements ◽  
Parameter Ranges ◽  
Process Material

Abstract This paper describes a web-based process/material advisory system that can be used during conceptual design. Given a set of design requirements for a part during conceptual design stage, our system produces process sequences that can meet the design requirements. Quite often during conceptual design stage, design requirements are not precisely defined. Therefore, we allow users to describe design requirements in terms of parameter ranges. Parameter ranges are used to capture uncertainties in design requirements. Our system accounts for uncertainties in design requirements in generating and evaluating process/material combinations. Our system uses a two step algorithm. During the first step, we generate a material/process option tree. This tree represents various process/material options that can be used to meet the given set of design requirements. During the second step, we evaluate various alternative process/material options using a depth first branch and bound algorithm to identify and recommend the least expensive process/material combination to the designer. Our system can be accessed on the World Wide Web using a standard browser. Our system allows designs to consider a wide variety of process/material options during the conceptual design stage and allows them to find the most cost-effective combination. By selecting the process/material combination during the early design stages, designers can ensure that the detailed design is compatible with all of the process constraints for the selected process.

scholarly journals The IDentif.AI 2.0 Pandemic Readiness Platform: Rapid Prioritization of Optimized COVID-19 Combination Therapy Regimens

2021 ◽  
Author(s):  
Agata Blasiak ◽  
Anh TL Truong ◽  
Alexandria Remus ◽  
Lissa Hooi ◽  
Shirley Gek Kheng Seah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Efficacy ◽  
Drug Combinations ◽  
Multiple Drug ◽  
Original Strain ◽  
Live Virus ◽  
Drug Synergy ◽  
Positive Treatment ◽  
Strong Candidate ◽  
Combination Regimens

Objectives: We aimed to harness IDentif.AI 2.0, a clinically actionable AI platform to rapidly pinpoint and prioritize optimal combination therapy regimens against COVID-19. Methods: A pool of starting candidate therapies was developed in collaboration with a community of infectious disease clinicians and included EIDD-1931 (metabolite of EIDD-2801), baricitinib, ebselen, selinexor, masitinib, nafamostat mesylate, telaprevir (VX-950), SN-38 (metabolite of irinotecan), imatinib mesylate, remdesivir, lopinavir, and ritonavir. Following the initial drug pool assessment, a focused, 6-drug pool was interrogated at 3 dosing levels per drug representing nearly 10,000 possible combination regimens. IDentif.AI 2.0 paired prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus (propagated, original strain and B.1.351 variant) and Vero E6 assay with a quadratic optimization workflow. Results: Within 3 weeks, IDentif.AI 2.0 realized a list of combination regimens, ranked by efficacy, for clinical go/no-go regimen recommendations. IDentif.AI 2.0 revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived. Conclusions: IDentif.AI 2.0 rapidly revealed promising drug combinations for a clinical translation. It pinpointed dose-dependent drug synergy behavior to play a role in trial design and realizing positive treatment outcomes. IDentif.AI 2.0 represents an actionable path towards rapidly optimizing combination therapy following pandemic emergence.

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