Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies.
Antibodies, Monoclonal
/ immunology
Antibodies, Monoclonal, Humanized
/ immunology
Antibodies, Neutralizing
/ immunology
COVID-19
/ immunology
Drug Repositioning
/ methods
Epitopes
/ immunology
Humans
Ipilimumab
/ immunology
Molecular Docking Simulation
SARS-CoV-2
/ drug effects
Spike Glycoprotein, Coronavirus
/ immunology
COVID-19 Drug Treatment
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 05 2021
13 05 2021
Historique:
received:
06
01
2021
accepted:
29
04
2021
entrez:
14
5
2021
pubmed:
15
5
2021
medline:
29
5
2021
Statut:
epublish
Résumé
The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications.
Identifiants
pubmed: 33986382
doi: 10.1038/s41598-021-89621-6
pii: 10.1038/s41598-021-89621-6
pmc: PMC8119408
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Antibodies, Neutralizing
0
Epitopes
0
Ipilimumab
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
tremelimumab
QEN1X95CIX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10220Subventions
Organisme : Robert Bosch Center for Data Science and Artificial Inelligence (RBCDSAI), Indian Institute of Technology Madras
ID : SB/20-21/0601/BT/RBCX/008473
Références
Bioinformatics. 2009 Jun 1;25(11):1422-3
pubmed: 19304878
Dev Comp Immunol. 2003 Jan;27(1):55-77
pubmed: 12477501
Nucleic Acids Res. 2019 Jan 8;47(D1):D464-D474
pubmed: 30357411
Life Sci. 2020 Sep 1;256:117883
pubmed: 32497632
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4
pubmed: 32425269
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Proteins. 2017 Mar;85(3):435-444
pubmed: 27936493
MAbs. 2016 Oct;8(7):1259-1268
pubmed: 27392298
J Phys Chem Lett. 2020 Nov 19;11(22):9781-9787
pubmed: 33147968
Nat Rev Immunol. 2020 Jun;20(6):345-346
pubmed: 32358580
Lancet. 2020 Feb 22;395(10224):565-574
pubmed: 32007145
JAMA. 2021 Mar 9;325(10):1015
pubmed: 33544136
Lancet. 2020 May 9;395(10235):1517-1520
pubmed: 32311318
Bioinformatics. 2019 Oct 15;35(20):4168-4169
pubmed: 30874800
Eur Respir J. 2020 Sep 3;56(3):
pubmed: 32616599
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219
pubmed: 32391667
AAPS J. 2018 Dec 13;21(1):9
pubmed: 30547287
Methods. 2017 Dec 1;131:33-65
pubmed: 28958951
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
Nat Rev Microbiol. 2009 Mar;7(3):226-36
pubmed: 19198616
Nat Commun. 2020 Jul 14;11(1):3518
pubmed: 32665542
J Med Virol. 2020 Jul;92(7):814-818
pubmed: 32253759
JCI Insight. 2020 Oct 15;5(20):
pubmed: 32937615
Science. 2020 Aug 7;369(6504):731-736
pubmed: 32540900
Bioinformatics. 2014 Aug 15;30(16):2288-94
pubmed: 24753488
Nat Rev Immunol. 2020 Sep;20(9):529-536
pubmed: 32728222
Cell Mol Immunol. 2020 Oct;17(10):1095-1097
pubmed: 32895485
Semin Oncol. 2010 Oct;37(5):450-4
pubmed: 21074059
Brief Bioinform. 2020 Sep 25;21(5):1549-1567
pubmed: 31626279
Cell Discov. 2020 Mar 16;6:14
pubmed: 32194980
Emerg Microbes Infect. 2020 Dec;9(1):313-319
pubmed: 32020836
Mol Immunol. 2013 Jan;53(1-2):24-34
pubmed: 22784991
Infection. 2021 Apr;49(2):199-213
pubmed: 32886331
Nucleic Acids Res. 2020 Jan 8;48(D1):D383-D388
pubmed: 31555805
Nat Nanotechnol. 2020 Aug;15(8):630-645
pubmed: 32661375
Cytokine. 1999 Apr;11(4):257-66
pubmed: 10328864
Antiviral Res. 2020 Jun;178:104787
pubmed: 32251768
J Transl Med. 2020 Jun 3;18(1):222
pubmed: 32493510
Sci Immunol. 2020 Jul 15;5(49):
pubmed: 32669287
Front Immunol. 2020 Jul 10;11:1664
pubmed: 32754161
J Biomol Struct Dyn. 2021 Apr;39(7):2673-2678
pubmed: 32248766
Proteins. 1993 May;16(1):1-7
pubmed: 8497480
Med Hypotheses. 2020 Jul;140:109749
pubmed: 32339777
Curr Top Med Chem. 2020;20(24):2210-2220
pubmed: 32648845
Cell Mol Immunol. 2020 May;17(5):541-543
pubmed: 32203186
Bioinformatics. 2016 Jan 15;32(2):298-300
pubmed: 26424857
N Engl J Med. 2020 Nov 5;383(19):1813-1826
pubmed: 32445440
Immunity. 2000 Jul;13(1):37-45
pubmed: 10933393
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
Oncologist. 2013 Jun;18(6):733-43
pubmed: 23774827
Bioinformatics. 2021 May 5;37(5):734-735
pubmed: 32805021
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
Expert Opin Ther Targets. 2021 Jun;25(6):415-421
pubmed: 32941780
Intensive Care Med. 2020 Sep;46(9):1769-1771
pubmed: 32514592
Nature. 2020 Oct;586(7827):113-119
pubmed: 32707573
Eur Thyroid J. 2017 Jul;6(3):167-170
pubmed: 28785544