Drug repurposing for COVID-19: Approaches, challenges and promising candidates

Abstract

Traditional drug development and discovery has not kept pace with threats from emerging and re-emerging diseases such as Ebola virus, MERS-CoV and more recently, SARS-CoV-2. Among other reasons, the exorbitant costs, high attrition rate and extensive periods of time from research to market approval are the primary contributing factors to the lag in recent traditional drug developmental activities. Due to these reasons, drug developers are starting to consider drug repurposing (or repositioning) as a viable alternative to the more traditional drug development process. Drug repurposing aims to find alternative uses of an approved or investigational drug outside of its original indication. The key advantages of this approach are that there is less developmental risk, and it is less time-consuming since the safety and pharmacological profile of the repurposed drug is already established. To that end, various approaches to drug repurposing are employed. Computational approaches make use of machine learning and algorithms to model disease and drug interaction, while experimental approaches involve a more traditional wet-lab experiments. This review would discuss in detail various ongoing drug repurposing strategies and approaches to combat the current COVID-19 pandemic, along with the advantages and the potential challenges.

COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19

“…Subsequently, S is cleaved by the Transmembrane protease serine 2 (TMPRSS2) to provide the S2 subunit necessary for the membrane fusion 41 , 42 . The drug repurposing activity aimed at preventing this step of the viral infection points to blocking the protein targets ACE2 and TMPRSS2, or to raising the endosomal pH in order to prevent the S processing 6 . To retrieve information on drugs in clinical trial for this purpose, we can highlight the target nodes Angiotensin-converting enzyme 2 and Transmembrane protease serine 2 in the DT network of COVIDrugNet and check the “Inspected targets” table below for drugs reported to bind those targets.…”

“…Known drugs that are currently in clinical or pre-clinical study for the treatment of COVID-19 are aimed either at inhibiting viral or human targets involved in some of the processes of viral entry and replication, or at treating inflammation and tissue injury consequent to the viral infection 5 , 6 . Even though it might seem that a direct antiviral approach could lead to a straightforward solution, only few of the existing antivirals have performed well in the clinic so far.…”

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

“…Among these three steps, the first step-the screening and identification of drugs with a high potential for repurposing-is the most crucial. As such, drug repositioning has two alternative and complementary approaches: an experiment-based approach and a theoretical or in silico-based approach, as shown in Figure 1 [26][27][28].…”

“…Among these three steps, the first step-the screening and identification of drugs with a high potential for repurposing-is the most crucial. As such, drug repositioning has two alternative and complementary approaches: an experimentbased approach and a theoretical or in silico-based approach, as shown in Figure 1 [26][27][28]. The experiment-based approach, also known as activity-based repositioning, refers to screening original drugs for new pharmacological applications based on experimental assays.…”

Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method

“…FDA-approved drugs with known safety and clinical profile allow for the reposition of drugs in the treatment of COVID-19. Despite the challenges that accompany drug repurposing, the ability to identify new uses of old drugs in a relatively short time is a significant incentive to focus on drug reposition for COVID-19 [1]. In the search for anti-SARS-CoV-2 molecules, various computational methods were applied combined with experimental approaches, and thousands of articles were published [2].…”