Drug Repurposing for Antivirals

In-vitro Methods for Drug Repurposing in AntiViral Therapy

Author(s): Narendra Vijay Tirpude and Anamika Sharma *

Pp: 78-120 (43)

DOI: 10.2174/9798898811143125010006

* (Excluding Mailing and Handling)

Abstract

 Emerging viral and re-emerging epidemic viral infectious diseases continued by global commerce, travel, and ecological system alteration are of public health concern. Despite concerted efforts and successful vaccination in limiting viral infections, humans are still terribly losing the battle against the microbes. Persisting pandemics, acquisition of drug resistance, and emerging and re-emerging microbes impose challenges and add substantial time and costs to develop broad-spectrum antivirals, which ultimately leads to prolonged hospital stays and doctor visits and increases global mortality. In this regard, drug repurposing is a great way to find new applications for already-approved therapies that circumvent numerous time-consuming experiments as well as financial costs associated with novel drug development. Screening of drugs directly using animals or via in-vivo method is challenging, timeconsuming, and expensive, which limits the assessment and re-use of already available drugs for repurposing. In-vitro drug testing is a vital stage in the drug discovery process and also reduces animal usage. To date, several in-vitro approaches are in use for the screening of new anti-viral agents and already approved strategies for drug repurposing. In-vitro anti-viral testing of compounds or any available market drug can assess the potential effectiveness in the pre-clinical model of anti-infective and deliver imperative information to determine the best combination ratios and dosing schedule. This chapter summarizes different traditional as well as modern in-vitro (biochemical and cell-based a) methods viz. TCID50, EC50 /CC50, Plaque, HAI assays (hemagglutination inhibition), ELISA/Luminex, Plaque-Reduction Neutralization Tests (PRNTs), plaque assays, or RT-PCR analysis, cytopathic effect (CPE)-based drug screening, and a high-throughput, high-content Automated Plaque Reduction (APR) used for the repurposing of drugs as anti-viral agents. Additionally, the chapter will provide the shortcomings, advantages and challenges of these modern and traditional methods. Information regarding the plant extracts, their active constituents, available marketed drugs, and compounds from different sources, which were remedies for different pathologies and were repurposed as anti-virals by using these methods, is also compiled.


Keywords: Antivirals, Cell-based assays, Cell-based techniques, Preclinical evaluation, Viral diseases.

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