Drug Repurposing Against SARS-CoV2

Table of Contents

• Ruchi Chawla, Varsha Rani, Krishan Kumar and Mohini Mishra
• Introduction
• Drug Repurposing Strategies
• Experimental Approaches
• Target Associated Screening/Binding Assays to Identify Target Candidate
• Phenotype-Based Repurposing
• Clinical Approaches
• Computational Approaches
• Re-Profiling of Drugs Based on Target / Molecular Docking
• Knowledge-Based
• Signature Based
• Pathway Based Repurposing
• Target-Mechanism-Based Repurposing
• Therapeutic Potential of Repurposing of Drugs for Lifethreatening Diseases
• Advantages of Drug Repurposing
• Cost and Time Minimization
• Accessibility of Information Related to the Drug for Development of Repurposed Drug
• Dosing Strength and Frequency
• Therapeutic Potential of Repurposed Drugs for the Treatment of Life-Threatening Diseases
• Tuberculosis
• Cancer
• Pulmonary Diseases
• Cardiac Diseases
• Antiviral Infections
• Renal Dysfunction
• Implications and Importance of Repurposing Drugs During Pandemic Outbreaks
• Conclusion
• Consent for Publication
• Conflict of Interest
• Acknowledgements
• References

• Malti Dadheech and Anand Kumar Maurya
• Introduction
• Potential Candidates for Adjuvant Therapy
• Vitamin D
• Stilbenoids
• Curcumin
• Zinc (Zn)
• Melatonin
• Iron Chelators
• Vitamin C
• Challenges Related to Drug Repurposing
• Limited Repository of Drugs
• Limited Efficacy of Repurposed Drugs
• Regulatory and Patent Considerations
• Accessibility of Data and Compound
• Uncertainty of Space for Repurposing Drugs
• Intellectual Property and Economic Considerations
• Ethical Issues Related to Drug Repurposing
• Regional Limitations of Clinical Research Ethics During Emergency Situations
• Fairness in Resource Distribution for Repurposed Drugs in Emergency Situations
• Involuntary Risk Burden
• Regulatory Aspects and Ethical Issues in Drug Repurposing for Covid-19
• Conclusion
• Consent for Publication
• Conflict of Interest
• Acknowledgements
• References

• Introduction
• Sars-Cov-2 Genome Structure
• Sars-Cov-2 Infection and Pathogenesis
• Sars-Cov-2 Genome Replication and Transcription
• Repurposed Drugs Against Sars-Cov-2 Replication
• Prevention of Sars-Cov-2 Entry into the Host Cell
• Nafamostat/Camostat
• Umifenovir
• Anti-Viral Approach by Targeting the Sars-Cov-2 Protease
• Lopinavir/Ritonavir
• Inhibition of Viral Rna Replicase
• Remdesivir
• Favipiravir
• Ribavirin
• Penciclovir
• Conclusion
• Future Perspective
• Consent for Publication
• Conflict of Interest
• Acknowledgements
• References

• Manisha Mulchandani, Amit Kumar Palai, Anjali Bhosale, Farhan Mazahir and Awesh K. Yadav
• Introduction
• Drug Repurposing
• Remdesivir
• Favipiravir
• Lopinavir and Ritonavir
• Hydroxychloroquine and Chloroquine
• Tocilizumab
• Darunavir
• Ribavirin
• Arbidol
• Camostat Mesylate
• Nafamostat
• Sofosbuvir
• Cepharanthine
• Nelfinavir
• Fluoxetine
• Enfuvirtide
• Role of Phytochemicals
• Drugs Repurposing Approaches
• Machine Learning-Based
• Genetic Association
• Retrospecting Clinical Analysis
• Structure-Based
• Pathway Based
• Signature Based
• Artificial Intelligence-Based
• Experimental Approaches
• Target-Based
• Binding Assay
• Drug-Centric
• Phenotype Based
• Drug Repurposing Scenarios in Antiviral Drug Discovery
• Same Target - New Virus
• Same Target New Indication
• New Target New Indications
• Animal Models in Sars-Cov-2 Repurposing
• Limitation of Identified Repurposed Molecules
• Personalized Drug Repurposing
• Conclusion
• Consent for Publication
• Conflict of Interest
• Acknowledgements
• References

• Introduction
• Mechanism of Pathogenesis in Covid-19
• Sars-Cov-2 Structure and Mutation
• Sars-Cov-2 Pathogenesis
• Various Pro-Inflammatory Cytokines as Target of Repurposed Drugs
• Cytokines, Types and Cytokine Storm
• Cytokines
• Cytokine Storm (Cs)
• Covid-19-Associated Cytokine Storm
• Pro-Inflammatory Cytokines
• Interleukins
• Transforming Growth Factor (Tnf)
• Interferons (Ifn)
• Granulocyte-Macrophage Colony-Stimulating Factor (Gm-Csf)
• Drugs Repurposing
• Repurposed Drugs Targeting Pro-Inflammatory Cytokines
• Targeting Induction of Coagulation in Covid-19 Patients
• Covid-19 Related Coagulopathy
• Endothelial Dysfunction and Covid-19
• Coagulation Test Analysis
• Venous Thromboembolic Prophylaxis
• Microvascular Thrombosin
• Clinical Interventions for Therapeutic Anticoagulation
• Conclusion
• Consent for Publication
• Conflict of Interest
• Acknowledgements
• References

• Tejal Shreeya and Tabish Qidwai
• Introduction
• High Throughput Screening
• Compound Library
• Methods of Hts
• Biochemical Assays
• Radiometric Assays
• Spa (Scintillating Proximity Assay)
• Flashplate Assay
• Fluorescence Assays
• Fluorescence Anisotropy and Fluorescence Polarization (Fa/Fp)
• Fluorescence Resonance Energy Transfer (Fret)
• Time Resolves Fluorescence Resonance Energy Transfer (Tr-Fret)
• Fluorescence Correlation Spectroscopy
• Binding Based Assays
• Fragment-Based Drug Design (Fbdd)
• Cell-Based Assays
• The Cell Viability Assay
• Reporter Gene Assay
• Second Messenger Assay
• Two Hybrid Screening
• Protein Fragment Complementation Assay
• Ultra High Throughput Screening (Uhts)
• Contents Preface

• Introduction to Statistics
• Introduction
• Data Types
• Sample Data
• Conclusion

• Introduction
• Frequency Distributions and Histograms
• Graphs
• Conclusion

• Introduction
• Samples Events and Their Probabilities
• Sample Spaces
• Event
• Examples
• Example 1
• Example 2
• Example 3
• Example 4
• Experiment
• Definition:
• Example 5
• Probability
• Examples
• Example 1
• Example 2
• Example 3
• Example 4
• Example 5
• Complements, Intersections, and Unions
• Complement
• Examples
• Example 1
• Probability Rule for Complements
• Example 2
• Intersection of Events
• Examples
• Example 1
• Example 2
• Probability Rule for Mutually Exclusive Events
• Example
• Union of Events
• Examples
• Example 1
• Example 2
• Additive Rule of Probability
• Example 3
• Example 4
• Example 5
• Conditional Probability and Independent Occurrences
• Conditional Probability
• Examples
• Example 1
• Example 2
• Example 3
• Independent Events
• Examples
• Example 1
• Example 2
• Example 3
• Example 4
• Probability in Tree Diagrams
• Example
• Principles
• Conclusion

• Introduction
• Random Variables
• Understanding Random Variables
• Types of Random Variables
• Example of Random Variable
• Example:
• Examples of Probability Distributions for Discrete Random Variables (Drv)
• Example 1
• Example 2
• Examples
• Example # 1
• Example # 2
• Example # 3
• Variance of Discrete Random Variables
• Characteristics and Notations
• Binominal Distribution
• Understanding Binominal Distribution
• Analyzing Binominal Distribution
• Criteria for Binominal Distribution
• Examples of Binominal Distributions
• Trial 1
• Trial 2
• Trial 3
• Cumulative Binominal Probability
• Negative Binominal Distribution
• Notations
• The Mean of Negative Binominal Distribution
• Conclusion

• Introduction
• Probability Distribution of Continuous Random Variable
• Properties
• Probability Density Functions
• Cumulative Distribution Functions
• Examples of Probability Distribution of Continuous Random Variable
• Example # 1
• The Normal Distribution
• Understanding Normal Distribution
• Kurtosis and Skewness
• Central Limit Theorem
• Sample Mean
• Convergence to Normal Distribution
• The Standard Normal Distribution
• The Standard Normal Distribution Vs. Normal Distribution
• Standardizing Normal Distribution
• How to Calculate Z-Score
• Example of Finding Z -Score
• To Find Probability Using the Normal Standard Distribution
• P Values and Z-Tests
• How to Use Z-Table
• Example: Using Z Distribution to Find Probability
• Areas of Tails of Distribution
• Tails of Standard Normal Distribution
• Conclusion

• Introduction
• The Mean and Standard Deviation (Sd) of the Sample Mean
• Examples
• Example 1
• Example 2
• The Sampling Distribution of the Sample Mean
• The Central Limit Theorem
• Examples
• Example 1
• Example 2
• Solution [44]
• Example 3
• Example 4
• Normally Distributed Populations
• Standard Deviation of X¯ (Standard Error) [44]
• Z-Score of the Sample Mean [44]
• Examples
• Example 1
• Example 2
• Example 3
• The Sample Proportion
• Sample Proportions in a Small Population:
• The Sampling Distribution of the Sample Proportion
• Examples
• Example 1
• Example 2
• Example 3
• Conclusion

• Introduction
• Construction of Confidence Intervals
• Interval Estimate Vs. Point Estimate
• Intervals of Confidence
• Confidence Level
• The Error Margin
• Estimator
• Interval Vs. Point Estimator
• Types of Estimators
• What is Standard Error (Sde)?
• Standard Deviation (Sd) of Sample Estimates
• Standard Error (Se) of Sample Estimates
• Margin of Error
• How to Calculate the Error Margin
• What is the Critical Value and How Do I Find It?
• What is a Confidence Interval, and How Does It Work?
• Confidence Intervals and How to Interpret Them
• Data Requirements for Confidence Interval
• What is a Confidence Interval, and How Do I Make One?
• Bias and Error
• Mse Stands for Mean Squared Error
• Sample Size and Estimates
• Determining the Sample Size is Necessary to Estimate the Population Mean
• Examples
• Example
• Large Sample Estimation of a Population Mean
• Large Sample 100 (1 - Α) % Confidence Interval for a Population Mean
• Example
• Small Sample Estimation of a Population Mean
• Small Sample 100 (1 -Α) % Confidence Interval for a Population Mean [53]
• Example 1
• Example 2
• Determining Sample Size Required to Estimate Population Proportion (P)
• Example
• Estimating the Target Parameter: Point Estimation
• Maximum Likelihood
• Linear Least Squares (Lls)
• Estimating the Target Parameter: Interval Estimation
• Example
• The T Distribution
• Estimating a Population Proportion
• Using Confidence Intervals to Determine the Population Proportion
• Examples
• Contents Foreword

Author

• Tabish Qidwai