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Evening the Score: Targeting SARS-CoV-2 Protease Inhibition in Graph Generative Models for Therapeutic Candidates [article]

Jenna Bilbrey, Logan Ward, Sutanay Choudhury, Neeraj Kumar, Ganesh Sivaraman
2021 arXiv   pre-print
We examine a pair of graph generative models for the therapeutic design of novel drug candidates targeting SARS-CoV-2 viral proteins.  ...  This generative framework[https://github.com/exalearn/covid-drug-design] will accelerate drug discovery in future pandemics through the high-throughput generation of targeted therapeutic candidates.  ...  In the current work, we develop, evaluate, and compare two leading graph-generative approaches to design candidate therapeutic compounds targeting SARS-CoV-2 protease inhibition ( Figure 1 ).  ... 
arXiv:2105.10489v1 fatcat:km7o3zdlzzdb5a4kavpstiisji

Predicting inhibitors for SARS-CoV-2 RNA-dependent RNA polymerase using machine learning and virtual screening [article]

Romeo Cozac
2020 arXiv   pre-print
We also performed virtual screening analysis of the drug candidates predicted by machine learning models and docked them against the active site of SARS- CoV-2 RdRp, a key component of the virus replication  ...  Further analysis of these candidates using molecular docking against the SARS-CoV-2 RdRp revealed low binding energies against the enzyme active site.  ...  algorithms have the potential to bind and inhibit the SARS-CoV-2 RdRp even though only ligand information was used to train those models.  ... 
arXiv:2006.06523v1 fatcat:klut5oomx5cv3gmt5xwlpzoake

Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs [article]

Sumanta Ray, Snehalika Lall, Anirban Mukhopadhyay, Sanghamitra Bandyopadhyay, Alexander Schönhuth
2020 arXiv   pre-print
Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies.  ...  Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising  ...  MG132 inhibits the cysteine protease m-calpain, which results in a pronounced inhibition of SARS-CoV-2 replication in the host cell.  ... 
arXiv:2007.02338v1 fatcat:a36qe7pawfehjh57o6szdbz3yi

Repurposing of Drugs for SARS-CoV-2 Using Inverse Docking Fingerprints

Marko Jukič, Katarina Kores, Dušanka Janežič, Urban Bren
2021 Frontiers in Chemistry  
A structure-based virtual screening of the FDA-approved drug database on SARS-CoV-2 main protease was performed, and the 11 highest-scoring compounds with known 3CLpro activity were identified while the  ...  In this way, the target-hitting space was examined and compared and we can support the further biological evaluation of all 11 newly reported hits on SARS-CoV-2 3CLpro as well as recommend further in-depth  ...  ACKNOWLEDGMENTS We gratefully acknowledge the support of NVIDIA Corporation with the donation of GPU hardware that was used in this research.  ... 
doi:10.3389/fchem.2021.757826 pmid:35028304 pmcid:PMC8748264 fatcat:cfsrtetbpvebzmvtk72mqtou6q

Identification of (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach

Jubie Selvaraj, Shyam Sundar P, Logesh Rajan, Divakar Selvaraj, Dhanabal Palanisamy, Krishnan Namboori PK, Suresh Kumar Mohankumar
2021 RSC Advances  
We acknowledge the generous infrastructure and research supports from JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty.  ...  Acknowledgements The authors are grateful to ALTEM Technologies private Ltd for providing an evaluation license for COVID-19 research and Ms.  ...  substituted 2-chloroquinoxaline frame work as lead compounds for Covid therapy. 10, 11 The present work evaluated the druggability of the SARS-CoV-2 main protease (SARS-CoV-2 M pro ) as a potential target  ... 
doi:10.1039/d1ra01603b pmid:35423848 pmcid:PMC8697517 fatcat:4j52bn7qivb4bamtcu4zu3x3oi

A critical overview of computational approaches employed for COVID-19 drug discovery

Eugene N. Muratov, Rommie Amaro, Carolina H. Andrade, Nathan Brown, Sean Ekins, Denis Fourches, Olexandr Isayev, Dima Kozakov, José L. Medina-Franco, Kenneth M. Merz, Tudor I. Oprea, Vladimir Poroikov (+7 others)
2021 Chemical Society Reviews  
We cover diverse methodologies, computational approaches, and case studies illustrating the ongoing efforts to develop viable drug candidates for treatment of COVID-19.  ...  assay; PPE: SARS-CoV-2 pseudo particle entry assay; M pro : RFET-based SARS-CoV-2 main protease inhibition assay. by achieving B30% success rate in the discovery of novel antivirals.  ...  SBDD studies with key SARS-CoV-2 targets Most of the SBDD research involving SARS-CoV-2 proteome has been focused on three main targets: the Spike glycoprotein (S-protein); papain-like protease (PLpro)  ... 
doi:10.1039/d0cs01065k pmid:34212944 pmcid:PMC8371861 fatcat:n6dxyyjxifh6hoehd7myapjtwu

Biomedical Text Link Prediction for Drug Discovery: A Case Study with COVID-19

Kevin McCoy, Sateesh Gudapati, Lawrence He, Elaina Horlander, David Kartchner, Soham Kulkarni, Nidhi Mehra, Jayant Prakash, Helena Thenot, Sri Vivek Vanga, Abigail Wagner, Brandon White (+1 others)
2021 Pharmaceutics  
The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, served as a case study to demonstrate the efficacy of link prediction modeling for drug discovery  ...  The link prediction algorithm guided identification and ranking of repurposed drug candidates for SARS-CoV-2 primarily by text mining biomedical literature from previous coronaviruses, including SARS and  ...  The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.  ... 
doi:10.3390/pharmaceutics13060794 pmid:34073456 fatcat:na32tnt62jcwxomlk6pger6sdq

Artificial Intelligence for COVID-19 Drug Discovery and Vaccine Development

Arash Keshavarzi Arshadi, Julia Webb, Milad Salem, Emmanuel Cruz, Stacie Calad-Thomson, Niloofar Ghadirian, Jennifer Collins, Elena Diez-Cecilia, Brendan Kelly, Hani Goodarzi, Jiann Shiun Yuan
2020 Frontiers in Artificial Intelligence  
To facilitate applications of deep learning for SARS-COV-2, we highlight multiple molecular targets of COVID-19, inhibition of which may increase patient survival.  ...  SARS-COV-2 has roused the scientific community with a call to action to combat the growing pandemic.  ...  ACKNOWLEDGMENTS We thank Farnam Kavehei for designing the figure. Also, we thank Melana Francisco for her contribution to the introduction of the article.  ... 
doi:10.3389/frai.2020.00065 pmid:33733182 pmcid:PMC7861281 fatcat:w6veg3bbanaj5fmzepdualoo2u

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

Vicky Mody, Joanna Ho, Savannah Wills, Ahmed Mawri, Latasha Lawson, Maximilian C. C. J. C. Ebert, Guillaume M. Fortin, Srujana Rayalam, Shashidharamurthy Taval
2021 Communications Biology  
In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV  ...  Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2.  ...  Further information on research design is available in the Nature Research Reporting Summary linked to this article. Table 1 and structural analysis for Fig. 6 ).  ... 
doi:10.1038/s42003-020-01577-x pmid:33473151 fatcat:7sqiwfatkvc77eozj4z73b3xhi

Computational screening for potential drug candidates against the SARS-CoV-2 main protease

Bruno Silva Andrade, Preetam Ghosh, Debmalya Barh, Sandeep Tiwari, Raner José Santana Silva, Wagner Rodrigues de Assis Soares, Tarcisio Silva Melo, Andria Santos Freitas, Patrícia González-Grande, Lucas Sousa Palmeira, Luiz Carlos Junior Alcantara, Marta Giovanetti (+2 others)
2020 F1000Research  
Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity.  ...  The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses  ...  provision and operation of computational facilities and the commitment to invest in Research & Development.  ... 
doi:10.12688/f1000research.23829.2 fatcat:uw2jk5cm7rbbvarngttka66mwu

The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies

Vaishali P Waman, Neeladri Sen, Mihaly Varadi, Antoine Daina, Shoshana J Wodak, Vincent Zoete, Sameer Velankar, Christine Orengo
2020 Briefings in Bioinformatics  
These include (i) understanding differences between SARS-CoV-2 and SARS-CoV, leading to increased infectivity of SARS-CoV-2, (ii) deciphering key residues in the SARS-CoV-2 involved in receptor–antibody  ...  Since the discovery of SARS-CoV-2, several structures of its proteins have been determined experimentally at an unprecedented speed and deposited in the Protein Data Bank.  ...  /vaccine candidates, serving as the foundation for designing the next generation of coronavirus therapeutics.  ... 
doi:10.1093/bib/bbaa362 pmid:33348379 fatcat:24w5gfkifrc35ohdcpl5chmpka

A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2

Shiwei Wang, Qi Sun, Youjun Xu, Jianfeng Pei, Luhua Lai
2021 Briefings in Bioinformatics  
As a proof-of-concept, we experimentally tested seven high-scored compounds that also demonstrated good binding strength in docking studies against the 3C-like protease of SARS-CoV-2 and found one novel  ...  Then, we applied transfer learning to fine-tune the model with the recently reported anti-SARS-CoV-2 compounds and derived a SARS-CoV-2 specific prediction model COVIDVS-3.  ...  We would like to thank Chenjing Cai for her help in transfer learning technique.  ... 
doi:10.1093/bib/bbab211 pmid:34081143 pmcid:PMC8195169 fatcat:j76lmi7hdfgqnkg3vcgza6tm4m

Machine intelligence design of 2019-nCoV drugs [article]

Duc Duy Nguyen, Kaifu Gao, Rui Wang, Guowei Wei
2020 biorxiv/medrxiv  
Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target.  ...  Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%.  ...  The authors thank Zihe Rao & Haitao Yang group at Shanghai Technological University for providing the crystal structure of 2019-nCoV 3CL hydrolase (PDB ID 6lu7) and thank Dr.  ... 
doi:10.1101/2020.01.30.927889 pmid:32511308 pmcid:PMC7217289 fatcat:xrj7xmpuprgtrfcfaog2pmitvu

Deep learning identifies synergistic drug combinations for treating COVID-19

Wengong Jin, Jonathan M. Stokes, Richard T. Eastman, Zina Itkin, Alexey V. Zakharov, James J. Collins, Tommi S. Jaakkola, Regina Barzilay
2021 Proceedings of the National Academy of Sciences of the United States of America  
We empirically validated our model predictions and discovered two drug combinations, remdesivir and reserpine as well as remdesivir and IQ-1S, which display strong antiviral SARS-CoV-2 synergy in vitro  ...  However, discovering single-agent therapies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been challenging.  ...  We thank all colleagues from NCATS for providing all the training data and screening the predicted drug combinations. We also thank Anne  ... 
doi:10.1073/pnas.2105070118 pmid:34526388 fatcat:gwf32plspndppin5ccyi74iy54

Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

Sanjana R Sen, Emily C Sanders, Kristin N Gabriel, Brian M Miller, Hariny M Isoda, Gabriela S Salcedo, Jason E Garrido, Rebekah P Dyer, Rie Nakajima, Aarti Jain, Ana-Maria Caldaruse, Alicia M Santos (+7 others)
2021 mSphere  
To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age.  ...  Such information could guide more effective therapeutic intervention.IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide.  ...  (Beijing, China) for expression and purification of COVAM antigens used in this study.  ... 
doi:10.1128/msphere.00203-21 pmid:33910993 fatcat:qyitbpqbrnerrdy3bs7qupxk3e
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