Learning from history: do not flatten the curve of antiviral research!

Bobrowski, Tesia; Melo-Filho, Cleber C.; Korn, Daniel; Alves, Vinícius M.; Popov, Konstantin; Auerbach, Scott S.; Schmitt, Charles; Moorman, Nathaniel J.; Muratov, Eugene; Tropsha, Alexander

doi:10.1016/j.drudis.2020.07.008

Cited by 29 publications

(27 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It took considerable research investments and six years for approval of azidothymidine, the first antiretroviral drug in the fight against HIV, originally synthetized for use as a cancer treatment agent, and even longer until highly effective antiretroviral therapies were available. 7 We are just at the beginning of our human interaction with corona virus diseases and since cross-species transmission of viral pathogens has emerged as a threat to humans, 8 a sustained investment in antiviral research can better prepare us for the future. Our repurposing of today's antiviral drug discoveries fuels hope of more rapid solutions to future viral pandemics that are inevitable.…”

Section: Therapeuticsmentioning

confidence: 99%

Viral pandemics and oral health: Lessons learned from HIV to SARS-CoV-2

Patton¹

2021

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

View full text Add to dashboard Cite

Section: Therapeuticsmentioning

confidence: 99%

Viral pandemics and oral health: Lessons learned from HIV to SARS-CoV-2

Patton¹

2021

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

View full text Add to dashboard Cite

“…In 2020, humanity encountered a new global threat, the pandemic of Corona Virus Disease 19 (COVID-19), an infectious disease caused by the SARS-CoV-2 virus. In response to this challenge, many researchers worldwide rapidly initiated the search for medicines that could block the virus interaction with the human organism and its infectivity [7]. We are participating in the Joint European Disruptive Initiative (JEDI) "Grand Challenge against COVID-19" [33].…”

Section: Identification Of New Potential Anti-sar-cov-2 Agentsmentioning

confidence: 99%

Computational Approaches to Identify a Hidden Pharmacological Potential in Large Chemical Libraries

Druzhilovskiy

Stolbov

Savosina

et al. 2020

JSFI

View full text Add to dashboard Cite

To improve the discovery of more effective and less toxic pharmaceutical agents, large virtual repositories of synthesizable molecules have been generated to increase the explored chemicalpharmacological space diversity. Such libraries include billions of structural formulae of druglike molecules associated with data on synthetic schemes, required building blocks, estimated physical-chemical parameters, etc. Clearly, such repositories are "Big Data". Thus, to identify the most promising compounds with the required pharmacological properties (hits) among billions of available opportunities, special computational methods are necessary. We have proposed using a combined computational approach, which combines structural similarity assessment, machine learning, and molecular modeling. Our approach has been validated in a project aimed at finding new pharmaceutical agents against HIV/AIDS and associated comorbidities from the Synthetically Accessible Virtual Inventory (SAVI), a 1.75 billion compound database. Potential inhibitors of HIV-1 protease and reverse transcriptase and agonists of toll-like receptors and STING, affecting innate immunity, were computationally identified. The activity of the three synthesized compounds has been confirmed in a cell-based assay. These compounds belong to the chemical classes, in which the agonistic effect on TLR 7/8 had not been previously shown. Synthesis and biological testing of several dozens of compounds with predicted antiretroviral activity are currently taking place at the NCI/NIH. We also carried out virtual screening among one billion substances to find compounds potentially possessing anti-SARS-CoV-2 activity. The selected hits' information has been accepted by the European Initiative "JEDI Grand Challenge against COVID-19" for synthesis and further biological evaluation. The possibilities and limitations of the approach are discussed.

show abstract

“…With over 35 million cases and over 1 million deaths worldwide as of the beginning of October, 2020, and no Food and Drug Administration (FDA) approved drug treatments or vaccines against this virus, there are unprecedented global efforts to discover critical therapeutic treatments against COVID-19 [1]. These efforts already resulted in the identification and characterization of many SARS-CoV-2 proteins essential for virus replication [2] and the pathogenesis of COVID-19 [3] and nomination of many drugs for clinical trials.…”

Section: Background and Significancementioning

confidence: 99%

COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

Korn¹,

Pervitsky²,

Bobrowski³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Objective: The COVID-19 pandemic has catalyzed a widespread effort to identify drug candidates and biological targets of relevance to SARS-COV-2 infection, which resulted in large numbers of publications on this subject. We have built the COVID-19 Knowledge Extractor (COKE), a web application to extract, curate, and annotate essential drug-target relationships from the research literature on COVID-19 to assist drug repurposing efforts. Materials and Methods: SciBiteAI ontological tagging of the COVID Open Research Dataset (CORD-19), a repository of COVID-19 scientific publications, was employed to identify drug-target relationships. Entity identifiers were resolved through lookup routines using UniProt and DrugBank. A custom algorithm was used to identify co-occurrences of protein and drug terms, and confidence scores were calculated for each entity pair. Results: COKE processing of the current CORD-19 database identified about 3,000 drug-protein pairs, including 29 unique proteins and 500 investigational, experimental, and approved drugs. Some of these drugs are presently undergoing clinical trials for COVID-19. Discussion: The rapidly evolving situation concerning the COVID-19 pandemic has resulted in a dramatic growth of publications on this subject in a short period. These circumstances call for methods that can condense the literature into the key concepts and relationships necessary for insights into SARS-CoV-2 drug repurposing. Conclusion: The COKE repository and web application deliver key drug - target protein relationships to researchers studying SARS-CoV-2. COKE portal may provide comprehensive and critical information on studies concerning drug repurposing against COVID-19. COKE is freely available at <a href="https://coke.mml.unc.edu/">https://coke.mml.unc.edu/</a> and the code is available at <a href="https://github.com/DnlRKorn/CoKE">https://github.com/DnlRKorn/CoKE</a>.

show abstract

Learning from history: do not flatten the curve of antiviral research!

Cited by 29 publications

References 27 publications

Viral pandemics and oral health: Lessons learned from HIV to SARS-CoV-2

Viral pandemics and oral health: Lessons learned from HIV to SARS-CoV-2

Computational Approaches to Identify a Hidden Pharmacological Potential in Large Chemical Libraries

COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

Contact Info

Product

Resources

About