Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning
Teena Bajaj, Babak Mosavati, Lydia H Zhang, Mohammad S Parsa, Huanchen Wang, Evan M Kerek, Xueying Liang, Seyed Amir Tabatabaei Dakhili, Eddie Wehri, Silin Guo, Rushil N Desai, Lauren M Orr, Mohammad R K Mofrad, Julia Schaletzky, John R Ussher, Xufang Deng, Robin Stanley, Basil P Hubbard, Daniel K Nomura, Niren Murthy
RSC Advances, doi:10.1039/d4ra06955b
Non-structural protein 15 (Nsp15) is a SARS-CoV-2 (SCoV-2) endoribonuclease and is a promising target for drug development because of its essential role in evading the host immune system. However, developing inhibitors against Nsp15 has been challenging due to its structural complexity and large RNA binding surface. In this report, we screened a 2640 acrylamide-based compound library against Nsp15 and identified 10 fragments that reacted with cysteine residues on Nsp15 and inhibited its endoribonuclease activity with IC 50 s less than 5 mM. These compounds had several attractive properties, such as low molecular weight (180-300 g mol -1 ), log P <3, zero violations to Lipinski's rules, and no apparent panassay interference (PAINs) properties. In addition, based on this data as a training set, we developed an artificial intelligence (AI) model that accelerated the hit to lead process and had a 73% accuracy for predicting new acrylamide-based Nsp15 inhibitors. Collectively, these results demonstrate that acrylamide fragments have great potential for developing Nsp15 inhibitors.
Author contributions
Conflicts of interest There are no conicts to declare.
References
Bakchi, Krishna, Sreecharan, Ganesh, Niharika et al., None, J. Mol. Struct
Ballarotto, Willems, Stiller, Nawa, Marschner et al., None, J. Med. Chem
Bhardwaj, Sun, Holzenburg, Guarino, Kao, None, J. Mol. Biol
Boike, Henning, Nomura, None, Nat. Rev. Drug Discovery
Borra, Lotufo, Gagioti, Barros Fde, Andrade, None, Braz. Oral Res
Bunally, Luscombe, Young, None, SLAS Discovery
Chen, Abou Farraj, Limonta, Dakhili, Kerek et al., None, J. Biol. Chem
Chen, Farraj, Limonta, Tabatabaei Dakhili, Kerek et al., None, J. Biol. Chem
Chen, Turcinovic, Feng, Kenney, Chin et al., None, iScience
Choi, Zhou, Shek, Wilson, Tillery et al., None, PLoS One
Daina, Michielin, Zoete, None, Sci. Rep
Daina, Zoete, None, ChemMedChem
Davids, Brown, None, Future Oncol
Deng, Hackbart, Mettelman, O'brien, Mielech et al., None, Proc. Natl. Acad. Sci. U. S. A
Duan, Zhou, Liu, Iketani, Lin et al., None, Nature
Dudas, Miteva, None, Trends Pharmacol. Sci
Frazier, Wilson, Krahn, Butay, Dillard et al., None, Nucleic Acids Res
Garcia-Sosa, Maran, Hetenyi, None, Curr. Med. Chem
Grisoni, None, Curr. Opin. Struct. Biol
Han, Hubbard, Lee, Montagna, Lee et al., None, Cell Cycle
Hashemian, Sheida, Taghizadieh, Memar, Hamblin et al., None, Biomed. Pharmacother
Hu, Lewandowski, Tan, Zhang, Morgan et al., None, ACS Cent. Sci
Jumper, Evans, Pritzel, Green, Figurnov et al., None, Nature
Karanl, Çol Ayvaz, ¸ahin, None, J. Mol. Struct
Kathman, Statsyuk, None, MedChemComm
Kim, Wower, Maltseva, Chang, Jedrzejczak et al., None, Commun. Biol
Kindler, Gil-Cruz, Spanier, Li, Wilhelm et al., None, PLoS Pathog
Lane, Urbina, Zhang, Fye, Gerlach et al., None, Mol. Pharm
Lanman, Allen, Allen, Amegadzie, Ashton et al., None, J. Med. Chem
Lipinski, Lombardo, Dominy, Feeney, None, Adv. Drug Delivery Rev
Liu, Pan, Zhang, Li, Ma et al., None, Lancet Reg. Health West. Pac
Martin, None, J. Med. Chem
Meng, Goddard, Pettersen, Couch, Pearson et al., None, Protein Sci
Moghadasi, Heilmann, Khalil, Nnabuife, Kearns et al., None, Sci. Adv
Ortiz-Alcantara, Bhardwaj, Palaninathan, Frieman, Baric et al., None, Virus Adapt. Treat
Parasuraman, None, J. Pharmacol. Pharmacother
Park, Aslanian, Mcclatchy, Han, Shah et al., None, Bioinformatics
Park, Venable, Xu, Yates, None, Nat. Methods
Pauly, Kumar, Singh, Kumar, Singh et al., None, Curr. Pharm. Des
Pettersen, Goddard, Huang, Meng, Couch et al., None, Protein Sci
Pillon, Frazier, Dillard, Williams, Kocaman et al., None, Nat. Commun
Pozzi, Vanet, Francesconi, Tagliazucchi, Tassone et al., None, J. Med. Chem
Protti, Rodrigues, Fonseca, Alves, De Oliveira et al., None, ChemMedChem
Reichel, Lienau, None, Handb. Exp. Pharmacol
Resnick, Bradley, Gan, Douangamath, Krojer et al., None, J. Am. Chem. Soc
Roos, Wu, Damm, Reboul, Stevenson et al., None, J. Chem. Theory Comput
Sutanto, Konstantinidou, Dömling, None, RSC Med. Chem
Søndergaard, Olsson, Rostkowski, Jensen, None, J. Chem. Theory Comput
Tabb, Mcdonald, Yates 3rd, None, J. Proteome Res
Tabb, Mcdonald, Yates, None, J. Proteome Res
Tropsha, Isayev, Varnek, Schneider, Cherkasov, None, Nat. Rev. Drug Discovery
Tu, Fu, Zheng, Xu, Gou et al., None, J. Chem. Inf. Model
Turon, Hlozek, Woodland, Kumar, Chibale et al., None, Nat. Commun
Van Loy, Stevaert, Naesens, None, Antiviral Res
Veber, Johnson, Cheng, Smith, Ward et al., None, J. Med. Chem
Vert, None, Nat. Biotechnol
Walter, Sjin, Haringsma, Ohashi, Sun et al., None, Cancer Discovery
Wang, Tian, Wang, Wang, Sun et al., None, Front. Pharmacol
Wong, Zheng, Valeri, Donghia, Anahtar et al., None, Nature
Xiong, Wu, Yi, Fu, Yang et al., None, Nucleic Acids Res
Xu, Park, Venable, Wohlschlegel, Diedrich et al., None, J. Proteomics
Xu, Venable, Park, Cociorva, Lu et al., None, Mol. Cell. Proteomics
Yuen, Lam, Wong, Mak, Wang et al., None, Emerging Microbes Infect
Zhang, Ji, Chen, He, Sun et al., None, iScience
Zhu, Li, Pang, None, Asian J. Pharm. Sci
Ábrányi-Balogh, Petri, Imre, Szijj, Scarpino et al., None, Eur. J. Med. Chem
DOI record:
{
"DOI": "10.1039/d4ra06955b",
"ISSN": [
"2046-2069"
],
"URL": "http://dx.doi.org/10.1039/d4ra06955b",
"abstract": "<jats:p>This study presented a novel screening of acrylamides discovering them as inhibitors against Nsp15 from SARS-CoV-2 and utilizing the data to develop an AI model to screen more inhibitors virtually.</jats:p>",
"author": [
{
"affiliation": [
{
"name": "Graduate Program of Comparative Biochemistry, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Bajaj",
"given": "Teena",
"sequence": "first"
},
{
"affiliation": [
{
"name": "Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA"
},
{
"name": "Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Mosavati",
"given": "Babak",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Graduate Program of Molecular Toxicology, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Zhang",
"given": "Lydia H.",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-3416-739X",
"affiliation": [
{
"name": "Department of Applied Science and Technology, University of California, Berkeley, CA, USA"
}
],
"authenticated-orcid": false,
"family": "Parsa",
"given": "Mohammad S.",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, North Carolina, USA"
}
],
"family": "Wang",
"given": "Huanchen",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Pharmacology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada"
}
],
"family": "Kerek",
"given": "Evan M.",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma Center for Respiratory and Infectious Disease, Oklahoma State University, Oklahoma, USA"
}
],
"family": "Liang",
"given": "Xueying",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"
}
],
"family": "Tabatabaei Dakhili",
"given": "Seyed Amir",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "The Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Wehri",
"given": "Eddie",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Guo",
"given": "Silin",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA"
}
],
"family": "Desai",
"given": "Rushil N.",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0009-0003-4326-5789",
"affiliation": [
{
"name": "Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA"
}
],
"authenticated-orcid": false,
"family": "Orr",
"given": "Lauren M.",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-7004-4859",
"affiliation": [
{
"name": "Department of Mechanical Engineering, University of California, Berkeley, CA, USA"
}
],
"authenticated-orcid": false,
"family": "Mofrad",
"given": "Mohammad R. K.",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "The Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, Berkeley, CA, USA"
},
{
"name": "The Molecular Therapeutics Initiative, University of California, Berkeley, 344 Li Ka Shing, Berkeley, CA, USA"
}
],
"family": "Schaletzky",
"given": "Julia",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"
}
],
"family": "Ussher",
"given": "John R.",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma Center for Respiratory and Infectious Disease, Oklahoma State University, Oklahoma, USA"
}
],
"family": "Deng",
"given": "Xufang",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, North Carolina, USA"
}
],
"family": "Stanley",
"given": "Robin",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-4353-9674",
"affiliation": [
{
"name": "Department of Pharmacology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada"
}
],
"authenticated-orcid": false,
"family": "Hubbard",
"given": "Basil P.",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-1614-8360",
"affiliation": [
{
"name": "Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA"
}
],
"authenticated-orcid": false,
"family": "Nomura",
"given": "Daniel K.",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-7815-7337",
"affiliation": [
{
"name": "Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma Center for Respiratory and Infectious Disease, Oklahoma State University, Oklahoma, USA"
}
],
"authenticated-orcid": false,
"family": "Murthy",
"given": "Niren",
"sequence": "additional"
}
],
"container-title": "RSC Advances",
"container-title-short": "RSC Adv.",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"rsc.org"
]
},
"created": {
"date-parts": [
[
2025,
4,
4
]
],
"date-time": "2025-04-04T08:42:21Z",
"timestamp": 1743756141000
},
"deposited": {
"date-parts": [
[
2025,
4,
4
]
],
"date-time": "2025-04-04T08:44:47Z",
"timestamp": 1743756287000
},
"funder": [
{
"DOI": "10.13039/100023782",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100023782",
"id-type": "DOI"
}
],
"name": "Henry Wheeler Center for Emerging and Neglected Diseases"
},
{
"DOI": "10.13039/100014220",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100014220",
"id-type": "DOI"
}
],
"name": "Innovative Genomics Institute"
},
{
"DOI": "10.13039/100000897",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000897",
"id-type": "DOI"
}
],
"name": "Cystic Fibrosis Foundation"
},
{
"DOI": "10.13039/100000066",
"award": [
"1ZIAES103340"
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000066",
"id-type": "DOI"
}
],
"name": "National Institute of Environmental Health Sciences"
},
{
"DOI": "10.13039/100000002",
"award": [
"UG3NS115599",
"R33",
"R61DA048444-01",
"RO1EB029320-01A1",
"RO1MH125979-01"
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000002",
"id-type": "DOI"
}
],
"name": "National Institutes of Health"
}
],
"indexed": {
"date-parts": [
[
2025,
4,
7
]
],
"date-time": "2025-04-07T04:04:56Z",
"timestamp": 1743998696237,
"version": "3.40.3"
},
"is-referenced-by-count": 0,
"issue": "13",
"issued": {
"date-parts": [
[
2025
]
]
},
"journal-issue": {
"issue": "13",
"published-print": {
"date-parts": [
[
2025,
3,
28
]
]
}
},
"language": "en",
"license": [
{
"URL": "http://creativecommons.org/licenses/by-nc/3.0/",
"content-version": "vor",
"delay-in-days": 92,
"start": {
"date-parts": [
[
2025,
4,
3
]
],
"date-time": "2025-04-03T00:00:00Z",
"timestamp": 1743638400000
}
}
],
"link": [
{
"URL": "http://pubs.rsc.org/en/content/articlepdf/2025/RA/D4RA06955B",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "292",
"original-title": [],
"page": "10243-10256",
"prefix": "10.1039",
"published": {
"date-parts": [
[
2025
]
]
},
"published-online": {
"date-parts": [
[
2025
]
]
},
"publisher": "Royal Society of Chemistry (RSC)",
"reference": [
{
"author": "Zhu",
"first-page": "4",
"journal-title": "Asian J. Pharm. Sci.",
"key": "D4RA06955B/cit1/1",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1021/acs.jmedchem.2c01229",
"author": "Pozzi",
"doi-asserted-by": "crossref",
"first-page": "3664",
"journal-title": "J. Med. Chem.",
"key": "D4RA06955B/cit2/1",
"volume": "66",
"year": "2023"
},
{
"DOI": "10.2174/1381612829666221107123841",
"author": "Pauly",
"doi-asserted-by": "crossref",
"first-page": "3677",
"journal-title": "Curr. Pharm. Des.",
"key": "D4RA06955B/cit3/1",
"volume": "28",
"year": "2022"
},
{
"DOI": "10.1016/j.biopha.2023.114367",
"author": "Hashemian",
"doi-asserted-by": "crossref",
"first-page": "114367",
"journal-title": "Biomed. Pharmacother.",
"key": "D4RA06955B/cit4/1",
"volume": "162",
"year": "2023"
},
{
"author": "Liu",
"first-page": "100694",
"journal-title": "Lancet Reg. Health West. Pac.",
"key": "D4RA06955B/cit5/1",
"volume": "33",
"year": "2023"
},
{
"DOI": "10.1038/s41586-023-06609-0",
"author": "Duan",
"doi-asserted-by": "crossref",
"first-page": "376",
"journal-title": "Nature",
"key": "D4RA06955B/cit6/1",
"volume": "622",
"year": "2023"
},
{
"DOI": "10.1126/sciadv.ade8778",
"author": "Moghadasi",
"doi-asserted-by": "crossref",
"first-page": "eade8778",
"journal-title": "Sci. Adv.",
"key": "D4RA06955B/cit7/1",
"volume": "9",
"year": "2023"
},
{
"author": "Deng",
"first-page": "E4251",
"journal-title": "Proc. Natl. Acad. Sci. U. S. A.",
"key": "D4RA06955B/cit8/1",
"volume": "114",
"year": "2017"
},
{
"DOI": "10.1371/journal.ppat.1006195",
"author": "Kindler",
"doi-asserted-by": "crossref",
"first-page": "e1006195",
"journal-title": "PLoS Pathog.",
"key": "D4RA06955B/cit9/1",
"volume": "13",
"year": "2017"
},
{
"DOI": "10.1016/j.isci.2023.107705",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "107705",
"journal-title": "iScience",
"key": "D4RA06955B/cit10/1",
"volume": "26",
"year": "2023"
},
{
"DOI": "10.1080/22221751.2020.1780953",
"author": "Yuen",
"doi-asserted-by": "crossref",
"first-page": "1418",
"journal-title": "Emerging Microbes Infect.",
"key": "D4RA06955B/cit11/1",
"volume": "9",
"year": "2020"
},
{
"DOI": "10.1101/2023.11.15.566945",
"author": "Otter",
"doi-asserted-by": "publisher",
"key": "D4RA06955B/cit12/1",
"unstructured": "C. J.Otter , N.Bracci , N. A.Parenti , C.Ye , L. H.Tan , A.Asthana , J. J.Pfannenstiel , N.Jackson , A. R.Fehr , R. H.Silverman , N. A.Cohen , L.Martinez-Sobrido and S. R.Weiss , bioRxiv , 2023 , preprint, 10.1101/2023.11.15.566945",
"volume-title": "bioRxiv",
"year": "2023"
},
{
"DOI": "10.1038/s41467-020-20608-z",
"author": "Pillon",
"doi-asserted-by": "crossref",
"first-page": "636",
"journal-title": "Nat. Commun.",
"key": "D4RA06955B/cit13/1",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1093/nar/gkac589",
"author": "Frazier",
"doi-asserted-by": "crossref",
"first-page": "8290",
"journal-title": "Nucleic Acids Res.",
"key": "D4RA06955B/cit14/1",
"volume": "50",
"year": "2022"
},
{
"DOI": "10.1038/s42003-021-01735-9",
"author": "Kim",
"doi-asserted-by": "crossref",
"first-page": "193",
"journal-title": "Commun. Biol.",
"key": "D4RA06955B/cit15/1",
"volume": "4",
"year": "2021"
},
{
"DOI": "10.1016/j.jbc.2023.105341",
"author": "Chen",
"doi-asserted-by": "crossref",
"first-page": "105341",
"journal-title": "J. Biol. Chem.",
"key": "D4RA06955B/cit16/1",
"volume": "299",
"year": "2023"
},
{
"author": "Ortiz-Alcantara",
"first-page": "125",
"journal-title": "Virus Adapt. Treat.",
"key": "D4RA06955B/cit17/1",
"volume": "2",
"year": "2010"
},
{
"DOI": "10.1039/D0MD00154F",
"author": "Sutanto",
"doi-asserted-by": "crossref",
"first-page": "876",
"journal-title": "RSC Med. Chem.",
"key": "D4RA06955B/cit18/1",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1016/j.ejmech.2018.10.010",
"author": "Ábrányi-Balogh",
"doi-asserted-by": "crossref",
"first-page": "94",
"journal-title": "Eur. J. Med. Chem.",
"key": "D4RA06955B/cit19/1",
"volume": "160",
"year": "2018"
},
{
"DOI": "10.1158/2159-8290.CD-13-0314",
"author": "Walter",
"doi-asserted-by": "crossref",
"first-page": "1404",
"journal-title": "Cancer Discovery",
"key": "D4RA06955B/cit20/1",
"volume": "3",
"year": "2013"
},
{
"DOI": "10.2217/fon.14.51",
"author": "Davids",
"doi-asserted-by": "crossref",
"first-page": "957",
"journal-title": "Future Oncol.",
"key": "D4RA06955B/cit21/1",
"volume": "10",
"year": "2014"
},
{
"DOI": "10.1021/acs.jmedchem.9b01180",
"author": "Lanman",
"doi-asserted-by": "crossref",
"first-page": "52",
"journal-title": "J. Med. Chem.",
"key": "D4RA06955B/cit22/1",
"volume": "63",
"year": "2019"
},
{
"DOI": "10.1038/s41573-022-00542-z",
"author": "Boike",
"doi-asserted-by": "crossref",
"first-page": "881",
"journal-title": "Nat. Rev. Drug Discovery",
"key": "D4RA06955B/cit23/1",
"volume": "21",
"year": "2022"
},
{
"DOI": "10.3389/fphar.2018.00353",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "353",
"journal-title": "Front. Pharmacol",
"key": "D4RA06955B/cit24/1",
"volume": "9",
"year": "2018"
},
{
"DOI": "10.1016/j.jmb.2006.06.021",
"author": "Bhardwaj",
"doi-asserted-by": "crossref",
"first-page": "243",
"journal-title": "J. Mol. Biol.",
"key": "D4RA06955B/cit25/1",
"volume": "361",
"year": "2006"
},
{
"DOI": "10.1371/journal.pone.0250019",
"author": "Choi",
"doi-asserted-by": "crossref",
"first-page": "e0250019",
"journal-title": "PLoS One",
"key": "D4RA06955B/cit26/1",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1039/C5MD00518C",
"author": "Kathman",
"doi-asserted-by": "crossref",
"first-page": "576",
"journal-title": "MedChemComm",
"key": "D4RA06955B/cit27/1",
"volume": "7",
"year": "2016"
},
{
"DOI": "10.1021/jacs.9b02822",
"author": "Resnick",
"doi-asserted-by": "crossref",
"first-page": "8951",
"journal-title": "J. Am. Chem. Soc.",
"key": "D4RA06955B/cit28/1",
"volume": "141",
"year": "2019"
},
{
"DOI": "10.4103/0976-500X.85932",
"author": "Parasuraman",
"doi-asserted-by": "crossref",
"first-page": "74",
"journal-title": "J. Pharmacol. Pharmacother.",
"key": "D4RA06955B/cit29/1",
"volume": "2",
"year": "2011"
},
{
"DOI": "10.1590/S1806-83242009000300006",
"author": "Borra",
"doi-asserted-by": "crossref",
"first-page": "255",
"journal-title": "Braz. Oral Res.",
"key": "D4RA06955B/cit30/1",
"volume": "23",
"year": "2009"
},
{
"DOI": "10.1007/164_2015_26",
"author": "Reichel",
"doi-asserted-by": "crossref",
"first-page": "235",
"journal-title": "Handb. Exp. Pharmacol.",
"key": "D4RA06955B/cit31/1",
"volume": "232",
"year": "2016"
},
{
"DOI": "10.1038/srep42717",
"author": "Daina",
"doi-asserted-by": "crossref",
"first-page": "42717",
"journal-title": "Sci. Rep.",
"key": "D4RA06955B/cit32/1",
"volume": "7",
"year": "2017"
},
{
"DOI": "10.1016/j.molstruc.2022.132712",
"author": "Bakchi",
"doi-asserted-by": "crossref",
"first-page": "132712",
"journal-title": "J. Mol. Struct.",
"key": "D4RA06955B/cit33/1",
"volume": "1259",
"year": "2022"
},
{
"DOI": "10.1177/2472555219859845",
"author": "Bunally",
"doi-asserted-by": "crossref",
"first-page": "791",
"journal-title": "SLAS Discovery",
"key": "D4RA06955B/cit34/1",
"volume": "24",
"year": "2019"
},
{
"DOI": "10.2174/092986712799945021",
"author": "Garcia-Sosa",
"doi-asserted-by": "crossref",
"first-page": "1646",
"journal-title": "Curr. Med. Chem.",
"key": "D4RA06955B/cit35/1",
"volume": "19",
"year": "2012"
},
{
"DOI": "10.1021/jm020017n",
"author": "Veber",
"doi-asserted-by": "crossref",
"first-page": "2615",
"journal-title": "J. Med. Chem.",
"key": "D4RA06955B/cit36/1",
"volume": "45",
"year": "2002"
},
{
"DOI": "10.1002/cmdc.201600182",
"author": "Daina",
"doi-asserted-by": "crossref",
"first-page": "1117",
"journal-title": "ChemMedChem",
"key": "D4RA06955B/cit37/1",
"volume": "11",
"year": "2016"
},
{
"DOI": "10.1002/cmdc.202000805",
"author": "Protti Í",
"doi-asserted-by": "crossref",
"first-page": "1446",
"journal-title": "ChemMedChem",
"key": "D4RA06955B/cit38/1",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1016/S0169-409X(00)00129-0",
"author": "Lipinski",
"doi-asserted-by": "crossref",
"first-page": "3",
"journal-title": "Adv. Drug Delivery Rev.",
"key": "D4RA06955B/cit39/1",
"volume": "46",
"year": "2001"
},
{
"DOI": "10.1021/jm0492002",
"author": "Martin",
"doi-asserted-by": "crossref",
"first-page": "3164",
"journal-title": "J. Med. Chem.",
"key": "D4RA06955B/cit40/1",
"volume": "48",
"year": "2005"
},
{
"DOI": "10.1093/nar/gkab255",
"author": "Xiong",
"doi-asserted-by": "crossref",
"first-page": "W5",
"journal-title": "Nucleic Acids Res.",
"key": "D4RA06955B/cit41/1",
"volume": "49",
"year": "2021"
},
{
"DOI": "10.1016/j.jbc.2023.105341",
"author": "Chen",
"doi-asserted-by": "crossref",
"first-page": "105341",
"issue": "11",
"journal-title": "J. Biol. Chem.",
"key": "D4RA06955B/cit42/1",
"volume": "299",
"year": "2023"
},
{
"DOI": "10.1016/j.molstruc.2021.131357",
"author": "Şahin",
"doi-asserted-by": "crossref",
"first-page": "131357",
"journal-title": "J. Mol. Struct.",
"key": "D4RA06955B/cit43/1",
"volume": "1248",
"year": "2021"
},
{
"DOI": "10.1016/j.antiviral.2024.105921",
"author": "Van Loy",
"doi-asserted-by": "crossref",
"first-page": "105921",
"journal-title": "Antiviral Res.",
"key": "D4RA06955B/cit44/1",
"volume": "228",
"year": "2024"
},
{
"DOI": "10.4161/cc.23056",
"author": "Han",
"doi-asserted-by": "crossref",
"first-page": "263",
"journal-title": "Cell Cycle",
"key": "D4RA06955B/cit45/1",
"volume": "12",
"year": "2013"
},
{
"DOI": "10.1016/j.isci.2023.106634",
"author": "Chen",
"doi-asserted-by": "crossref",
"first-page": "106634",
"journal-title": "iScience",
"key": "D4RA06955B/cit46/1",
"volume": "26",
"year": "2023"
},
{
"DOI": "10.1021/acscentsci.3c00538",
"author": "Hu",
"doi-asserted-by": "crossref",
"first-page": "1658",
"journal-title": "ACS Cent. Sci.",
"key": "D4RA06955B/cit47/1",
"volume": "9",
"year": "2023"
},
{
"author": "Xu",
"first-page": "S174",
"journal-title": "Mol. Cell. Proteomics",
"key": "D4RA06955B/cit48/1",
"volume": "5",
"year": "2006"
},
{
"DOI": "10.1016/j.jprot.2015.07.001",
"author": "Xu",
"doi-asserted-by": "crossref",
"first-page": "16",
"journal-title": "J. Proteomics",
"key": "D4RA06955B/cit49/1",
"volume": "129",
"year": "2015"
},
{
"DOI": "10.1021/pr015504q",
"author": "Tabb",
"doi-asserted-by": "crossref",
"first-page": "21",
"journal-title": "J. Proteome Res.",
"key": "D4RA06955B/cit50/1",
"year": "2002"
},
{
"DOI": "10.1021/pr015504q",
"author": "Tabb",
"doi-asserted-by": "crossref",
"first-page": "21",
"journal-title": "J. Proteome Res.",
"key": "D4RA06955B/cit51/1",
"volume": "1",
"year": "2002"
},
{
"DOI": "10.1038/nmeth.1195",
"author": "Park",
"doi-asserted-by": "crossref",
"first-page": "319",
"journal-title": "Nat. Methods",
"key": "D4RA06955B/cit52/1",
"volume": "5",
"year": "2008"
},
{
"DOI": "10.1093/bioinformatics/btu151",
"author": "Park",
"doi-asserted-by": "crossref",
"first-page": "2208",
"journal-title": "Bioinformatics",
"key": "D4RA06955B/cit53/1",
"volume": "30",
"year": "2014"
},
{
"DOI": "10.1021/ct200133y",
"author": "Søndergaard",
"doi-asserted-by": "crossref",
"first-page": "2284",
"journal-title": "J. Chem. Theory Comput.",
"key": "D4RA06955B/cit54/1",
"volume": "7",
"year": "2011"
},
{
"DOI": "10.1021/acs.jctc.8b01026",
"author": "Roos",
"doi-asserted-by": "crossref",
"first-page": "1863",
"journal-title": "J. Chem. Theory Comput.",
"key": "D4RA06955B/cit55/1",
"volume": "15",
"year": "2019"
},
{
"DOI": "10.1002/pro.4792",
"author": "Meng",
"doi-asserted-by": "crossref",
"first-page": "e4792",
"journal-title": "Protein Sci.",
"key": "D4RA06955B/cit56/1",
"volume": "32",
"year": "2023"
},
{
"DOI": "10.1002/pro.3943",
"author": "Pettersen",
"doi-asserted-by": "crossref",
"first-page": "70",
"journal-title": "Protein Sci.",
"key": "D4RA06955B/cit57/1",
"volume": "30",
"year": "2021"
},
{
"DOI": "10.1021/acs.molpharmaceut.2c00662",
"author": "Lane",
"doi-asserted-by": "crossref",
"first-page": "4320",
"journal-title": "Mol. Pharm.",
"key": "D4RA06955B/cit58/1",
"volume": "19",
"year": "2022"
},
{
"DOI": "10.1021/acs.jcim.3c01736",
"author": "Tu",
"doi-asserted-by": "crossref",
"first-page": "1433",
"journal-title": "J. Chem. Inf. Model.",
"key": "D4RA06955B/cit59/1",
"volume": "64",
"year": "2024"
},
{
"DOI": "10.1016/j.tips.2023.11.001",
"author": "Dudas",
"doi-asserted-by": "crossref",
"first-page": "39",
"journal-title": "Trends Pharmacol. Sci.",
"key": "D4RA06955B/cit60/1",
"volume": "45",
"year": "2024"
},
{
"DOI": "10.1038/s41586-023-06887-8",
"author": "Wong",
"doi-asserted-by": "crossref",
"first-page": "177",
"journal-title": "Nature",
"key": "D4RA06955B/cit61/1",
"volume": "626",
"year": "2024"
},
{
"DOI": "10.1038/s41587-023-01789-6",
"author": "Vert",
"doi-asserted-by": "crossref",
"first-page": "750",
"journal-title": "Nat. Biotechnol.",
"key": "D4RA06955B/cit62/1",
"volume": "41",
"year": "2023"
},
{
"DOI": "10.1038/s41467-023-41512-2",
"author": "Turon",
"doi-asserted-by": "crossref",
"first-page": "5736",
"journal-title": "Nat. Commun.",
"key": "D4RA06955B/cit63/1",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1016/j.sbi.2023.102527",
"author": "Grisoni",
"doi-asserted-by": "crossref",
"first-page": "102527",
"journal-title": "Curr. Opin. Struct. Biol.",
"key": "D4RA06955B/cit64/1",
"volume": "79",
"year": "2023"
},
{
"DOI": "10.1038/s41573-023-00832-0",
"author": "Tropsha",
"doi-asserted-by": "crossref",
"first-page": "141",
"journal-title": "Nat. Rev. Drug Discovery",
"key": "D4RA06955B/cit65/1",
"volume": "23",
"year": "2024"
},
{
"DOI": "10.1021/acs.jmedchem.3c00485",
"author": "Ballarotto",
"doi-asserted-by": "crossref",
"first-page": "8170",
"journal-title": "J. Med. Chem.",
"key": "D4RA06955B/cit66/1",
"volume": "66",
"year": "2023"
},
{
"DOI": "10.1038/s41586-021-03819-2",
"author": "Jumper",
"doi-asserted-by": "crossref",
"first-page": "583",
"journal-title": "Nature",
"key": "D4RA06955B/cit67/1",
"volume": "596",
"year": "2021"
}
],
"reference-count": 67,
"references-count": 67,
"relation": {
"has-review": [
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v1/review2",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v2/response1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v2/decision1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v1/review1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v2/review1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v2/review2",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v3/decision1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v3/response1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v1/decision1",
"id-type": "doi"
},
{
"asserted-by": "object",
"id": "10.1039/D4RA06955B/v3/review1",
"id-type": "doi"
}
]
},
"resource": {
"primary": {
"URL": "https://xlink.rsc.org/?DOI=D4RA06955B"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning",
"type": "journal-article",
"update-policy": "https://doi.org/10.1039/rsc_crossmark_policy",
"volume": "15"
}
