Drug Repurposing: A Strategy for Discovering Inhibitors against Emerging Viral Infections

Abstract

Background: Viral diseases are responsible for several deaths around the world. Over the past few years, the world has seen several outbreaks caused by viral diseases that for a long time seemed to possess no risk. These are diseases that have been forgotten for a long time and, until nowadays, there are no approved drugs or vaccines, leading the pharmaceutical industry and several research groups to run out of time in the search for new pharmacological treatments or prevention methods. In this context, drug repurposing proves to be a fast and economically viable technique, considering the fact that it uses drugs that have a well-established safety profile. Thus, in this review, we present the main advances in drug repurposing and their benefit for searching new treatments against emerging viral diseases. Methods: We conducted a search in the bibliographic databases (Science Direct, Bentham Science, PubMed, Springer, ACS Publisher, Wiley, and NIH’s COVID-19 Portfolio) using the keywords "drug repurposing", "emerging viral infections" and each of the diseases reported here (CoV; ZIKV; DENV; CHIKV; EBOV and MARV) as an inclusion/exclusion criterion. A subjective analysis was performed regarding the quality of the works for inclusion in this manuscript. Thus, the selected works were those that presented drugs repositioned against the emerging viral diseases presented here by means of computational, high-throughput screening or phenotype-based strategies, with no time limit and of relevant scientific value. Results: 291 papers were selected, 24 of which were CHIKV; 52 for ZIKV; 43 for DENV; 35 for EBOV; 10 for MARV; and 56 for CoV and the rest (72 papers) related to the drugs repurposing and emerging viral diseases. Among CoV-related articles, most were published in 2020 (31 papers), updating the current topic. Besides, between the years 2003 - 2005, 10 articles were created, and from 2011 - 2015 there were 7 articles, portraying the outbreaks that occurred at that time. For ZIKV, similar to CoV, most publications were during the period of outbreaks between the years 2016 - 2017 (23 articles). Similarly, most CHIKV (13 papers) and DENV (14 papers) publications occur at the same time interval. For EBOV (13 papers) and MARV (4 papers), they were between the years 2015 - 2016. Through this review, several drugs were highlighted that can be evolved in vivo and clinical trials as possible used against these pathogens showed that remdesivir represent potential treatments against CoV. Furthermore, ribavirin may also be a potential treatment against CHIKV; sofosbuvir against ZIKV; celgosivir against DENV, and favipiravir against EBOV and MARV, representing new hopes against these pathogens. Conclusions: The conclusions of this review manuscript show the potential of the drug repurposing strategy in the discovery of new pharmaceutical products, as from this approach, drugs that could be used against emerging viral diseases. Thus, this strategy deserves more attention among research groups and is a promising approach to the discovery of new drugs against emerging viral diseases and also other diseases.

Updates on Drug Designing Approach Through Computational Strategies: a Review

“…It involves evaluating drugs already approved by regulatory agencies such as the FDA to develop new uses, which can reduce the development time and costs associated with bringing new drugs to market. This approach offers opportunities to identify promising drug candidates that can be repurposed with the potential to improve the lives of patients [ 264–266 ]. Drug repurposing, also known as drug repositioning, is the process of discovering new therapeutic uses for existing drugs that are already approved for other indications [ 264 ].…”

Application of Computational Biology and Artificial Intelligence in Drug Design

“…CADD has until now led to the discovery of more than 70 approved drugs [ 4 ], from Captopril in 1981 [ 150 , 151 ] to Remdesivir in 2021 [ 152 ]. Two important categories of CADD, structure-based drug design (SBDD) and ligand-based drug design (LBDD), are highlighted in this review.…”

A new possible indication of direct-acting anti-hepatitis C drugs in the therapeutic management of COVID-19: A narrative literature review

“…35 Sofosbuvir is approved for the treatment of hepatitis C. Also, the drug has excellent results against other viruses like the ZIKV. 22 Sofosbuvir especially can be useful in the early phase of COVID-19 before the virus attacks the lung cells. 23 Recent studies showed that the active form of sofosbuvir terminates RdRp activity.…”

“…This study indicated that simeprevir was stable in the protease binding pocket and had suitable interaction with catalytic residues Cys145 and His41. 22 According to a molecular docking study conducted by Rahman et al 6 , simeprevir was introduced as one of the best candidates against SARS-CoV-2 Mpro. Simeprevir had several bonds with amino acid residues in addition to hydrogen bonds and electrostatic interactions.…”