Analysis of Chemical Spaces: Implications for Drug Repurposing

Orlov, Alexey A.; Berishvili, Vladimir; Nikitina, Anastasia; Osolodkin, Dmitry I.; Radchenko, Eugene V.; Palyulin, Vladimir A.

doi:10.1016/b978-0-12-816125-8.00013-4

“…Similarly, a notable number of articles related to the concept of chemical space are associated with drug repurposing (20). In particular, using network-based representations to predict drug-target interactions and more complex interactions, including drug-disease, protein-disease, and drug-side effect associations, to name a few [70].…”

Section: Meta-analysis Of Applications Of Chemical Spacementioning

confidence: 99%

Approaches for enhancing the analysis of chemical space for drug discovery

Saldívar-González

¹

,

Medina-Franco

²

2022

Expert Opinion on Drug Discovery

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Chemical space is a powerful, general, and practical conceptual framework in drug discovery and other areas in chemistry that addresses the diversity of molecules and it has various applications. Moreover, chemical space is a cornerstone of chemoinformatics as a scientific discipline. In response to the increase in the set of chemical compounds in databases, generators of chemical structures, and tools to calculate molecular descriptors, novel approaches to generate visual representations of chemical space in low dimensions are emerging and evolving. Such approaches include a wide range of commercial and free applications, software, and open-source methods. Herein, the current state of chemical space in drug design and discovery is reviewed. The topics discussed herein include advances for efficient navigation in chemical space, the use of this concept in assessing the diversity of different data sets, exploring structure-property/activity relationships for one or multiple endpoints, and compound library design. Recent advances in methodologies for generating visual representations of chemical space have been highlighted, thereby emphasizing open-source methods. It is concluded that quantitative and qualitative generation and analysis of chemical space require novel approaches for handling the increasing number of molecules and their information available in chemical databases (including emerging ultra-large libraries). In addition, it is of utmost importance to note that chemical space is a conceptual framework that goes beyond visual representation in low dimensions. However, the graphical representation of chemical space has several practical applications in drug discovery and beyond.

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

Nascimento

¹

,

Aquino

²

,

Silva-Júnior

³

2021

CMC

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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.

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Approaches for enhancing the analysis of chemical space for drug discovery

Saldívar-González

¹

,

Medina-Franco

²

2022

Preprint

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Chemical space is a powerful, general, and practical conceptual framework in drug discovery and other areas in chemistry that addresses the diversity of molecules and it has various applications. Moreover, chemical space is a cornerstone of chemoinformatics as a scientific discipline. In response to the increase in the set of chemical compounds in databases, generators of chemical structures, and tools to calculate molecular descriptors, novel approaches to generate visual representations of chemical space in low dimensions are emerging and evolving. Such approaches include a wide range of commercial and free applications, software, and open-source methods. Herein, the current state of chemical space in drug design and discovery is reviewed. The topics discussed herein include advances for efficient navigation in chemical space, the use of this concept in assessing the diversity of different data sets, exploring structure-property/activity relationships for one or multiple endpoints, and compound library design. Recent advances in methodologies for generating visual representations of chemical space have been highlighted, thereby emphasizing open-source methods. It is concluded that quantitative and qualitative generation and analysis of chemical space require novel approaches for handling the increasing number of molecules and their information available in chemical databases (including emerging ultra-large libraries). In addition, it is of utmost importance to note that chemical space is a conceptual framework that goes beyond visual representation in low dimensions. However, the graphical representation of chemical space has several practical applications in drug discovery and beyond.

show abstract

Analysis of Chemical Spaces: Implications for Drug Repurposing

Cited by 3 publications

References 181 publications

Approaches for enhancing the analysis of chemical space for drug discovery

Approaches for enhancing the analysis of chemical space for drug discovery

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

Approaches for enhancing the analysis of chemical space for drug discovery

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