Many small steps towards a COVID-19 drug

Erlanson, Daniel A.

doi:10.1038/s41467-020-18710-3

Cited by 20 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Remdesivir has been approved for COVID-19 treatment in the USA and many vaccine trials are at their last phase while the Pfizer vaccine has been approved for emergency use in some countries (at the time of writing this article). It has been noted that many small steps have been made in discovering clinically applicable drugs to treat COVID-19 ( Erlanson, 2020 ). It is anticipated that vaccines and antibody-based drugs will be discovered before small molecules.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Structural Basis of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

2021

View full text Add to dashboard Cite

The Coronavirus disease-19 (COVID-19) pandemic is still devastating the world causing significant social, economic, and political chaos. Corresponding to the absence of globally approved antiviral drugs for treatment and vaccines for controlling the pandemic, the number of cases and/or mortalities are still rising. Current patient management relies on supportive treatment and the use of repurposed drugs as an indispensable option. Of a crucial role in the viral life cycle, ongoing studies are looking for potential inhibitors to the main protease (Mpro) of severe acute respiratory syndrome Coronavirus -2 (SARS-CoV-2) to tackle the pandemic. Although promising results have been achieved in searching for drugs inhibiting the Mpro, work remains to be done on designing structure-based improved drugs. This review discusses the structural basis of potential inhibitors targeting SARS-CoV-2 Mpro, identifies gaps, and provides future directions. Further, compounds with potential Mpro based antiviral activity are highlighted.

show abstract

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Structural Basis of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

2021

View full text Add to dashboard Cite

show abstract

“…In order to screen FDA‐approved database, different structure‐based virtual screening approaches were used. Namely, three approaches were applied in initial SBVS: GRID molecular interaction fields (MIFs) fingerprint approach implemented in FLAP v.2.2 software; [34,35] Genetic algorithm based molecular docking in GOLD v.5.8.1; [36] Glide's (Schrödinger Release, 2020–2, limited liability company (LLC) [37–9] ) hierarchical docking strategy.…”

Section: Methodsmentioning

confidence: 99%

“…Although SARS‐CoV‐2 vaccines have been brought to the market, chemotherapeutic approaches still represent attractive strategy to combat SARS‐CoV‐2 [8] . Numerous small molecule drug discovery projects and clinical trials are in progress [9,10] . Clinical studies investigating efficacy and safety of the initially repurposed drugs (remdesivir, hydroxychloroquine, and lopinavir) reported conflicting results which justify further efforts in the field of drug repurposing [11–14] …”

Section: Introductionmentioning

confidence: 99%

An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

Djoković

Djikić

Cvijić

et al. 2021

Molecular Informatics

View full text Add to dashboard Cite

Aims: An infectious disease caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (M pro ). Main methods:To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association. Key findings:Through the presented approach, 43 candidates with potential inhibitory effect on M pro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.Significance: To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of M pro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.

show abstract

“…In practice, the available chemical material shows bias towards the most commonly used chemical reactions (192), however, it still the case that the XChem program delivers between 2% and 10% fragment hit rates (soaks yielding bound fragments in the structure) for projects amenable to multi-crystal soaking and screening by crystallography. A remarkable result exemplified by the more than 100 projects screened since 2016, including the successful screening and follow-up of the SARS-CoV-2 M pro protein, also released as an open science public service (193,194).…”

Section: Fragment Library Designmentioning

confidence: 99%

Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

et al. 2021

View full text Add to dashboard Cite

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.

show abstract

Many small steps towards a COVID-19 drug

Abstract: A large-scale screening campaign has yielded dozens of crystal structures of small molecule fragments that bind to the main protease of SARS-CoV-2. The global research community is encouraged to pursue these as drug discovery starting points for COVID-19.

Cited by 20 publications

References 16 publications

Structural Basis of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Structural Basis of Potential Inhibitors Targeting SARS-CoV-2 Main Protease

An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

Contact Info

Product

Resources

About