215 results on '"Andrade, Carolina H."'
Search Results
2. QSAR models for predicting cardiac toxicity of drugs
- Author
-
Sanches, Igor H., primary, Mendonca, Sabrina S., additional, Alves, Vinicius M., additional, Braga, Rodolpho C., additional, and Andrade, Carolina H., additional
- Published
- 2024
- Full Text
- View/download PDF
3. List of contributors
- Author
-
Akortia, Eric, primary, Alla, Sai Radha Mani, additional, Alves, Vinicius M., additional, Andrade, Carolina H., additional, Avram, Speranta, additional, Bao, Tong, additional, Benfenati, Emilio, additional, Braga, Rodolpho C., additional, Buiu, Catalin, additional, Chakravarti, Suman K., additional, Chen, Jingwen, additional, Chen, Minjun, additional, Ciura, Krzesimir, additional, Colombo, Erika, additional, Cross, Kevin P., additional, Cui, Shixuan, additional, del Giudice, Giusy, additional, Dong, Fan, additional, Duchowicz, Pablo R., additional, Egbi, Courage, additional, Egodawatta, Prasanna, additional, Elakkiya, Elango, additional, Federico, Antonio, additional, Fratello, Michele, additional, Fu, Zhiqiang, additional, Furuhama, Ayako, additional, Gao, Yuchen, additional, Garro Martinez, Juan C., additional, Gbeddy, Gustav, additional, Giner, Beatriz, additional, Glover, Eric, additional, Goonetilleke, Ashantha, additional, Greco, Dario, additional, Gromelski, Maciej, additional, Gu, Yaxin, additional, Gui, Binxin, additional, Guo, Jing, additional, Guo, Wenjing, additional, He, Jiale, additional, He, Minghui, additional, Hong, Huixiao, additional, Honma, Masamitsu, additional, Huang, Shuheng, additional, Huang, Ruili, additional, Huang, Meiling, additional, Jaeger, Martin, additional, Jillella, Gopala Krishna, additional, Johnson, Candice, additional, Kasamatsu, Toshio, additional, Khan, Pathan Mohsin, additional, Koster, Sander, additional, Kusko, Rebecca, additional, Lee, Myeongsang, additional, Li, Chao, additional, Li, Fei, additional, Li, Bohao, additional, Li, Menglong, additional, Li, Dongying, additional, Li, Jinjie, additional, Li, Xuehua, additional, Li, Zoe, additional, Liao, Tsung-Jen, additional, Liu, Yuan, additional, Liu, Huihui, additional, Liu, Jie, additional, Liu, Wenjia, additional, Lomba, Laura, additional, Lou, Chaofeng, additional, Ma, Guangcai, additional, Manganelli, Serena, additional, Mei, Hu, additional, Mendonca, Sabrina S., additional, Mizuno, Tadahaya, additional, Myatt, Glenn J., additional, Ngan, Deborah K., additional, Ning, Baitang, additional, Pandit, Shraddha, additional, Parthasarathi, Ramakrishnan, additional, Patterson, Tucker A., additional, Pavel, Alisa, additional, Prabhu, Paulraj, additional, Puzyn, Tomasz, additional, Qu, Jiao, additional, Roncaglioni, Alessandra, additional, Roy, Kunal, additional, Saarimäki, Laura Aliisa, additional, Saavedra, Laura M., additional, Sanches, Igor H., additional, Schilter, Benoit, additional, Selvaraj, Chandrabose, additional, Serra, Angela, additional, Shi, Wei, additional, Singh, Prakrity, additional, Singh, Sanjeev Kumar, additional, Sogor, Catalina, additional, Song, Meng, additional, Sosnowska, Anita, additional, Su, Limin, additional, Sugiyama, Kei-ichi, additional, Swirog, Marta, additional, Tang, Yun, additional, Teng, Yuefa, additional, Tong, Weida, additional, Tropsha, Alexander, additional, Udrea, Ana-Maria, additional, Velmurugan, Devadasan, additional, Voigt, Melanie, additional, Wang, Haobo, additional, Wang, Xiaoqing, additional, Wang, Zhongyu, additional, Wang, Xueyu, additional, Wei, Xiaoxuan, additional, Wen, Zhining, additional, Wu, Yiqu, additional, Wyrzykowska, Ewelina, additional, Xiao, Fang, additional, Xie, Hong-Bin, additional, Xu, Tuan, additional, Xu, Liang, additional, Yang, Xianhai, additional, Yu, Haiying, additional, Zhang, Yuxuan, additional, Zhang, Jiachen, additional, Zhao, Jingwen, additional, Zhao, Yuanhui, additional, Zhu, Minghua, additional, Zhuang, Shulin, additional, and Zou, Wen, additional
- Published
- 2024
- Full Text
- View/download PDF
4. Chalcones from Angelica keiskei (ashitaba) inhibit key Zika virus replication proteins
- Author
-
Mottin, Melina, Caesar, Lindsay K., Brodsky, David, Mesquita, Nathalya C.M.R., de Oliveira, Ketllyn Zagato, Noske, Gabriela Dias, Sousa, Bruna K.P., Ramos, Paulo R.P.S., Jarmer, Hannah, Loh, Bonnie, Zorn, Kimberley M., Foil, Daniel H., Torres, Pedro M., Guido, Rafael V.C., Oliva, Glaucius, Scholle, Frank, Ekins, Sean, Cech, Nadja B., Andrade, Carolina H., and Laster, Scott M.
- Published
- 2022
- Full Text
- View/download PDF
5. Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate
- Author
-
Freire, Marjorie C. L. C., Basso, Luis G. M., Mendes, Luis F. S., Mesquita, Nathalya C. M. R., Mottin, Melina, Fernandes, Rafaela S., Policastro, Lucca R., Godoy, Andre S., Santos, Igor A., Ruiz, Uriel E. A., Caruso, Icaro P., Sousa, Bruna K. P., Jardim, Ana C. G., Almeida, Fabio C. L., Gil, Laura H. V. G., Andrade, Carolina H., and Oliva, Glaucius
- Published
- 2022
- Full Text
- View/download PDF
6. Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes
- Author
-
Martins, Ligia F, Mesquita, Juliana T, Pinto, Erika G, Costa-Silva, Thais A, Borborema, Samanta ET, Galisteo, Andres J, Neves, Bruno J, Andrade, Carolina H, Shuhaib, Zainab Al, Bennett, Elliot L, Black, Gregory P, Harper, Philip M, Evans, Daniel M, Fituri, Hisham S, Leyland, John P, Martin, Claire, Roberts, Terence D, Thornhill, Andrew J, Vale, Stephen A, Howard-Jones, Andrew, Thomas, Dafydd A, Williams, Harri L, Overman, Larry E, Berlinck, Roberto GS, Murphy, Patrick J, and Tempone, Andre G
- Subjects
Health Sciences ,Traditional ,Complementary and Integrative Medicine ,Infectious Diseases ,Vector-Borne Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Alkaloids ,Animals ,Guanidines ,Leishmania infantum ,Marine Biology ,Molecular Structure ,Nitric Oxide ,Porifera ,Trypanosoma cruzi ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences ,Medicinal & Biomolecular Chemistry ,Traditional ,complementary and integrative medicine - Abstract
Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism.
- Published
- 2016
7. Pyrimidine Azepine Targets the Plasmodium bc1Complex and Displays Multistage Antimalarial Activity
- Author
-
Calit, Juliana, Prajapati, Surendra K., Benavente, Ernest D., Araújo, Jessica E., Deng, Bingbing, Miura, Kazutoyo, Annunciato, Yasmin, Moura, Igor M. R., Usui, Miho, Medeiros, Jansen F., Andrade, Carolina H., Silva-Mendonça, Sabrina, Simeonov, Anton, Eastman, Richard T., Long, Carole A., da Silva Araujo, Maisa, Williamson, Kim C., Aguiar, Anna Caroline C., and Bargieri, Daniel Y.
- Abstract
Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic Plasmodium bergheiline was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of PyAz90, the most potent pyrimidine azepine chemotype identified, against P. falciparumand P. vivaxin the asexual and sexual stages. PyAz90blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of P. falciparumPyAz90-resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome bas a molecular target of PyAz90. This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the Plasmodiumcytochrome bc1complex.
- Published
- 2024
- Full Text
- View/download PDF
8. Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria
- Author
-
Conserva, Geanne A. Alves, da Costa-Silva, Thais A., Amaral, Maiara, Antar, Guilherme M., Neves, Bruno J., Andrade, Carolina H., Tempone, Andre G., and Lago, João Henrique G.
- Published
- 2019
- Full Text
- View/download PDF
9. Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
- Author
-
Borba, Joyce V.B., Silva, Arthur C., Ramos, Pablo I.P., Grazzia, Nathalia, Miguel, Danilo C., Muratov, Eugene N., Furnham, Nicholas, and Andrade, Carolina H.
- Published
- 2019
- Full Text
- View/download PDF
10. Chemical toxicity prediction for major classes of industrial chemicals: Is it possible to develop universal models covering cosmetics, drugs, and pesticides?
- Author
-
Alves, Vinicius M., Muratov, Eugene N., Zakharov, Alexey, Muratov, Nail N., Andrade, Carolina H., and Tropsha, Alexander
- Published
- 2018
- Full Text
- View/download PDF
11. Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity
- Author
-
Tomaz, Kaira C. P., primary, Tavella, Tatyana A., additional, Borba, Joyce V. B., additional, Salazar-Alvarez, Luis C., additional, Levandoski, João E., additional, Mottin, Melina, additional, Sousa, Bruna K. P., additional, Moreira-Filho, José T., additional, Almeida, Vitor M., additional, Clementino, Leandro C., additional, Bourgard, Catarina, additional, Massirer, Katlin B., additional, Couñago, Rafael M., additional, Andrade, Carolina H., additional, Sunnerhagen, Per, additional, Bilsland, Elizabeth, additional, Cassiano, Gustavo C., additional, and Costa, Fabio T. M., additional
- Published
- 2023
- Full Text
- View/download PDF
12. Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages
- Author
-
Grecco, Simone S., Costa-Silva, Thais A., Jerz, Gerold, de Sousa, Fernanda S., Londero, Vinicius S., Galuppo, Mariana K., Lima, Marta L., Neves, Bruno J., Andrade, Carolina H., Tempone, Andre G., and Lago, João Henrique G.
- Published
- 2017
- Full Text
- View/download PDF
13. Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds
- Author
-
Sainas, Stefano, Pippione, Agnese C., Giorgis, Marta, Lupino, Elisa, Goyal, Parveen, Ramondetti, Cristina, Buccinnà, Barbara, Piccinini, Marco, Braga, Rodolpho C., Andrade, Carolina H., Andersson, Mikael, Moritzer, Ann-Christin, Friemann, Rosmarie, Mensa, Stefano, Al-Karadaghi, Salam, Boschi, Donatella, and Lolli, Marco L.
- Published
- 2017
- Full Text
- View/download PDF
14. Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi
- Author
-
Grecco, Simone S., Costa-Silva, Thais A., Jerz, Gerold, de Sousa, Fernanda S., Alves Conserva, Geanne A., Mesquita, Juliana T., Galuppo, Mariana K., Tempone, Andre G., Neves, Bruno J., Andrade, Carolina H., Cunha, Rodrigo L.O.R., Uemi, Miriam, Sartorelli, Patricia, and Lago, João Henrique G.
- Published
- 2017
- Full Text
- View/download PDF
15. Chapter 26 - QSAR models for predicting cardiac toxicity of drugs
- Author
-
Sanches, Igor H., Mendonca, Sabrina S., Alves, Vinicius M., Braga, Rodolpho C., and Andrade, Carolina H.
- Published
- 2024
- Full Text
- View/download PDF
16. Shortcuts to schistosomiasis drug discovery: The state-of-the-art
- Author
-
Moreira-Filho, José T., primary, Dantas, Rafael F., additional, Senger, Mário R., additional, Silva, Arthur C., additional, Campos, Dulcinea M.B., additional, Muratov, Eugene, additional, Silva-Junior, Floriano P., additional, Andrade, Carolina H., additional, and Neves, Bruno J., additional
- Published
- 2019
- Full Text
- View/download PDF
17. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds
- Author
-
Alves, Vinicius M., Muratov, Eugene, Fourches, Denis, Strickland, Judy, Kleinstreuer, Nicole, Andrade, Carolina H., and Tropsha, Alexander
- Published
- 2015
- Full Text
- View/download PDF
18. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization
- Author
-
Alves, Vinicius M., Muratov, Eugene, Fourches, Denis, Strickland, Judy, Kleinstreuer, Nicole, Andrade, Carolina H., and Tropsha, Alexander
- Published
- 2015
- Full Text
- View/download PDF
19. Biotransformation of LASSBio-579 and pharmacological evaluation of p-hydroxylated metabolite a N-phenylpiperazine antipsychotic lead compound
- Author
-
Gomes, Tatiana F., Pompeu, Thais E.T., Rodrigues, Daniel A., Noël, François, Menegatti, Ricardo, Andrade, Carolina H., Sabino, José R., Gil, Eric S., Dalla Costa, Teresa, Betti, Andresa H., Antonio, Camila B., Rates, Stela M.K., Fraga, Carlos A.M., Barreiro, Eliezer J., and de Oliveira, Valéria
- Published
- 2013
- Full Text
- View/download PDF
20. In silico metabolism studies of dietary flavonoids by CYP1A2 and CYP2C9
- Author
-
Sousa, Mariana C., Braga, Rodolpho C., Cintra, Bertilha A.S., de Oliveira, Valéria, and Andrade, Carolina H.
- Published
- 2013
- Full Text
- View/download PDF
21. Proteomic identification of metabolic changes in Paracoccidioides brasiliensisinduced by a nitroheteroarylchalcone
- Author
-
Júnior, Marcos ABC, Silva, Lívia C, Rocha, Olivia B, Oliveira, Amanda A, Portis, Igor G, Alonso, Antonio, Alonso, Lais, Silva, Kleber SF, Gomes, Marcelo N, Andrade, Carolina H, Soares, Célia MA, and Pereira, Maristela
- Abstract
Aim:To access the metabolic changes caused by a chalcone derivative (LabMol-75) through a proteomic approach. Methods:Proteomic analysis was performed after 9 h of Paracoccidioides brasiliensisyeast (Pb18) cell incubation with the LabMol-75at MIC. The proteomic findings were validated through in vitroand in silicoassays. Results:Exposure to the compound led to the downregulation of proteins associated with glycolysis and gluconeogenesis, β-oxidation, the citrate cycle and the electron transport chain. Conclusion:LabMol-75caused an energetic imbalance in the fungus metabolism and deep oxidative stress. Additionally, the in silicomolecular docking approach pointed to this molecule as a putative competitive inhibitor of DHPS.
- Published
- 2023
- Full Text
- View/download PDF
22. Erratum: CATMoS: Collaborative Acute Toxicity Modeling Suite
- Author
-
Mansouri, Kamel, primary, Karmaus, Agnes L., additional, Fitzpatrick, Jeremy, additional, Patlewicz, Grace, additional, Pradeep, Prachi, additional, Alberga, Domenico, additional, Alepee, Nathalie, additional, Allen, Timothy E.H., additional, Allen, Dave, additional, Alves, Vinicius M., additional, Andrade, Carolina H., additional, Auernhammer, Tyler R., additional, Ballabio, Davide, additional, Bell, Shannon, additional, Benfenati, Emilio, additional, Bhattacharya, Sudin, additional, Bastos, Joyce V., additional, Boyd, Stephen, additional, Brown, J. B., additional, Capuzzi, Stephen J., additional, Chushak, Yaroslav, additional, Ciallella, Heather, additional, Clark, Alex M., additional, Consonni, Viviana, additional, Daga, Pankaj R., additional, Ekins, Sean, additional, Farag, Sherif, additional, Fedorov, Maxim, additional, Fourches, Denis, additional, Gadaleta, Domenico, additional, Gao, Feng, additional, Gearhart, Jeffery M., additional, Goh, Garett, additional, Goodman, Jonathan M., additional, Grisoni, Francesca, additional, Grulke, Christopher M., additional, Hartung, Thomas, additional, Hirn, Matthew, additional, Karpov, Pavel, additional, Korotcov, Alexandru, additional, Lavado, Giovanna J., additional, Lawless, Michael, additional, Li, Xinhao, additional, Luechtefeld, Thomas, additional, Lunghini, Filippo, additional, Mangiatordi, Giuseppe F., additional, Marcou, Gilles, additional, Marsh, Dan, additional, Martin, Todd, additional, Mauri, Andrea, additional, Muratov, Eugene N., additional, Myatt, Glenn J., additional, Nguyen, Dac-Trung, additional, Nicolotti, Orazio, additional, Note, Reine, additional, Pande, Paritosh, additional, Parks, Amanda K., additional, Peryea, Tyler, additional, Polash, Ahsan H., additional, Rallo, Robert, additional, Roncaglioni, Alessandra, additional, Rowlands, Craig, additional, Ruiz, Patricia, additional, Russo, Daniel P., additional, Sayed, Ahmed, additional, Sayre, Risa, additional, Sheils, Timothy, additional, Siegel, Charles, additional, Silva, Arthur C., additional, Simeonov, Anton, additional, Sosnin, Sergey, additional, Southall, Noel, additional, Strickland, Judy, additional, Tang, Yun, additional, Teppen, Brian, additional, Tetko, Igor V., additional, Thomas, Dennis, additional, Tkachenko, Valery, additional, Todeschini, Roberto, additional, Toma, Cosimo, additional, Tripodi, Ignacio, additional, Trisciuzzi, Daniela, additional, Tropsha, Alexander, additional, Varnek, Alexandre, additional, Vukovic, Kristijan, additional, Wang, Zhongyu, additional, Wang, Liguo, additional, Waters, Katrina M., additional, Wedlake, Andrew J., additional, Wijeyesakere, Sanjeeva J., additional, Wilson, Dan, additional, Xiao, Zijun, additional, Yang, Hongbin, additional, Zahoranszky-Kohalmi, Gergely, additional, Zakharov, Alexey V., additional, Zhang, Fagen F., additional, Zhang, Zhen, additional, Zhao, Tongan, additional, Zhu, Hao, additional, Zorn, Kimberley M., additional, Casey, Warren, additional, and Kleinstreuer, Nicole C., additional
- Published
- 2021
- Full Text
- View/download PDF
23. Structural and chemical basis for enhanced affinity to a series of mycobacterial thymidine monophosphate kinase inhibitors: fragment-based QSAR and QM/MM docking studies
- Author
-
Bueno, Renata V., Toledo, Ney R., Neves, Bruno J., Braga, Rodolpho C., and Andrade, Carolina H.
- Published
- 2013
- Full Text
- View/download PDF
24. Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence
- Author
-
Moreira-Filho, José T, Silva, Arthur C, Dantas, Rafael F, Gomes, Barbara F, Souza Neto, Lauro R, Brandao-Neto, Jose, Owens, Raymond J, Furnham, Nicholas, Neves, Bruno J, Silva-Junior, Floriano P, and Andrade, Carolina H
- Subjects
parasitic diseases - Abstract
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.
- Published
- 2021
25. Combination of docking, molecular dynamics and quantum mechanical calculations for metabolism prediction of 3,4-methylenedioxybenzoyl-2-thienylhydrazone
- Author
-
Braga, Rodolpho C., Alves, Vinícius M., Fraga, Carlos A. M., Barreiro, Eliezer J., de Oliveira, Valéria, and Andrade, Carolina H.
- Published
- 2012
- Full Text
- View/download PDF
26. Fragment-based and classical quantitative structure–activity relationships for a series of hydrazides as antituberculosis agents
- Author
-
Andrade, Carolina H., Salum, Livia de B., Castilho, Marcelo S., Pasqualoto, Kerly F. M., Ferreira, Elizabeth I., and Andricopulo, Adriano D.
- Published
- 2008
- Full Text
- View/download PDF
27. A critical overview of computational approaches employed for COVID-19 drug discovery
- Author
-
Muratov, Eugene N., Amaro, Rommie, Andrade, Carolina H., Brown, Nathan, Ekins, Sean, Fourches, Denis, Isayev, Olexandr, Kozakov, Dima, Medina-Franco, Jose L., Merz, Kenneth M., Oprea, Tudor I., Poroikov, Vladimir, Schneider, Gisbert, Todd, Matthew H., Varnek, Alexandre, Winkler, David A., Zakharov, Alexey, Cherkasov, Artem, Tropsha, Alexander, Muratov, Eugene N., Amaro, Rommie, Andrade, Carolina H., Brown, Nathan, Ekins, Sean, Fourches, Denis, Isayev, Olexandr, Kozakov, Dima, Medina-Franco, Jose L., Merz, Kenneth M., Oprea, Tudor I., Poroikov, Vladimir, Schneider, Gisbert, Todd, Matthew H., Varnek, Alexandre, Winkler, David A., Zakharov, Alexey, Cherkasov, Artem, and Tropsha, Alexander
- Abstract
COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19.
- Published
- 2021
28. CATMoS: Collaborative Acute Toxicity Modeling Suite
- Author
-
Mansouri, K, Karmaus, A, Fitzpatrick, J, Patlewicz, G, Pradeep, P, Alberga, D, Alepee, N, Allen, T, Allen, D, Alves, V, Andrade, C, Auernhammer, T, Ballabio, D, Bell, S, Benfenati, E, Bhattacharya, S, Bastos, J, Boyd, S, Brown, J, Capuzzi, S, Chushak, Y, Ciallella, H, Clark, A, Consonni, V, Daga, P, Ekins, S, Farag, S, Fedorov, M, Fourches, D, Gadaleta, D, Gao, F, Gearhart, J, Goh, G, Goodman, J, Grisoni, F, Grulke, C, Hartung, T, Hirn, M, Karpov, P, Korotcov, A, Lavado, G, Lawless, M, Li, X, Luechtefeld, T, Lunghini, F, Mangiatordi, G, Marcou, G, Marsh, D, Martin, T, Mauri, A, Muratov, E, Myatt, G, Nguyen, D, Nicolotti, O, Note, R, Pande, P, Parks, A, Peryea, T, Polash, A, Rallo, R, Roncaglioni, A, Rowlands, C, Ruiz, P, Russo, D, Sayed, A, Sayre, R, Sheils, T, Siegel, C, Silva, A, Simeonov, A, Sosnin, S, Southall, N, Strickland, J, Tang, Y, Teppen, B, Tetko, I, Thomas, D, Tkachenko, V, Todeschini, R, Toma, C, Tripodi, I, Trisciuzzi, D, Tropsha, A, Varnek, A, Vukovic, K, Wang, Z, Wang, L, Waters, K, Wedlake, A, Wijeyesakere, S, Wilson, D, Xiao, Z, Yang, H, Zahoranszky-Kohalmi, G, Zakharov, A, Zhang, F, Zhang, Z, Zhao, T, Zhu, H, Zorn, K, Casey, W, Kleinstreuer, N, Mansouri, Kamel, Karmaus, Agnes L, Fitzpatrick, Jeremy, Patlewicz, Grace, Pradeep, Prachi, Alberga, Domenico, Alepee, Nathalie, Allen, Timothy E H, Allen, Dave, Alves, Vinicius M, Andrade, Carolina H, Auernhammer, Tyler R, Ballabio, Davide, Bell, Shannon, Benfenati, Emilio, Bhattacharya, Sudin, Bastos, Joyce V, Boyd, Stephen, Brown, J B, Capuzzi, Stephen J, Chushak, Yaroslav, Ciallella, Heather, Clark, Alex M, Consonni, Viviana, Daga, Pankaj R, Ekins, Sean, Farag, Sherif, Fedorov, Maxim, Fourches, Denis, Gadaleta, Domenico, Gao, Feng, Gearhart, Jeffery M, Goh, Garett, Goodman, Jonathan M, Grisoni, Francesca, Grulke, Christopher M, Hartung, Thomas, Hirn, Matthew, Karpov, Pavel, Korotcov, Alexandru, Lavado, Giovanna J, Lawless, Michael, Li, Xinhao, Luechtefeld, Thomas, Lunghini, Filippo, Mangiatordi, Giuseppe F, Marcou, Gilles, Marsh, Dan, Martin, Todd, Mauri, Andrea, Muratov, Eugene N, Myatt, Glenn J, Nguyen, Dac-Trung, Nicolotti, Orazio, Note, Reine, Pande, Paritosh, Parks, Amanda K, Peryea, Tyler, Polash, Ahsan H, Rallo, Robert, Roncaglioni, Alessandra, Rowlands, Craig, Ruiz, Patricia, Russo, Daniel P, Sayed, Ahmed, Sayre, Risa, Sheils, Timothy, Siegel, Charles, Silva, Arthur C, Simeonov, Anton, Sosnin, Sergey, Southall, Noel, Strickland, Judy, Tang, Yun, Teppen, Brian, Tetko, Igor V, Thomas, Dennis, Tkachenko, Valery, Todeschini, Roberto, Toma, Cosimo, Tripodi, Ignacio, Trisciuzzi, Daniela, Tropsha, Alexander, Varnek, Alexandre, Vukovic, Kristijan, Wang, Zhongyu, Wang, Liguo, Waters, Katrina M, Wedlake, Andrew J, Wijeyesakere, Sanjeeva J, Wilson, Dan, Xiao, Zijun, Yang, Hongbin, Zahoranszky-Kohalmi, Gergely, Zakharov, Alexey V, Zhang, Fagen F, Zhang, Zhen, Zhao, Tongan, Zhu, Hao, Zorn, Kimberley M, Casey, Warren, Kleinstreuer, Nicole C, Mansouri, K, Karmaus, A, Fitzpatrick, J, Patlewicz, G, Pradeep, P, Alberga, D, Alepee, N, Allen, T, Allen, D, Alves, V, Andrade, C, Auernhammer, T, Ballabio, D, Bell, S, Benfenati, E, Bhattacharya, S, Bastos, J, Boyd, S, Brown, J, Capuzzi, S, Chushak, Y, Ciallella, H, Clark, A, Consonni, V, Daga, P, Ekins, S, Farag, S, Fedorov, M, Fourches, D, Gadaleta, D, Gao, F, Gearhart, J, Goh, G, Goodman, J, Grisoni, F, Grulke, C, Hartung, T, Hirn, M, Karpov, P, Korotcov, A, Lavado, G, Lawless, M, Li, X, Luechtefeld, T, Lunghini, F, Mangiatordi, G, Marcou, G, Marsh, D, Martin, T, Mauri, A, Muratov, E, Myatt, G, Nguyen, D, Nicolotti, O, Note, R, Pande, P, Parks, A, Peryea, T, Polash, A, Rallo, R, Roncaglioni, A, Rowlands, C, Ruiz, P, Russo, D, Sayed, A, Sayre, R, Sheils, T, Siegel, C, Silva, A, Simeonov, A, Sosnin, S, Southall, N, Strickland, J, Tang, Y, Teppen, B, Tetko, I, Thomas, D, Tkachenko, V, Todeschini, R, Toma, C, Tripodi, I, Trisciuzzi, D, Tropsha, A, Varnek, A, Vukovic, K, Wang, Z, Wang, L, Waters, K, Wedlake, A, Wijeyesakere, S, Wilson, D, Xiao, Z, Yang, H, Zahoranszky-Kohalmi, G, Zakharov, A, Zhang, F, Zhang, Z, Zhao, T, Zhu, H, Zorn, K, Casey, W, Kleinstreuer, N, Mansouri, Kamel, Karmaus, Agnes L, Fitzpatrick, Jeremy, Patlewicz, Grace, Pradeep, Prachi, Alberga, Domenico, Alepee, Nathalie, Allen, Timothy E H, Allen, Dave, Alves, Vinicius M, Andrade, Carolina H, Auernhammer, Tyler R, Ballabio, Davide, Bell, Shannon, Benfenati, Emilio, Bhattacharya, Sudin, Bastos, Joyce V, Boyd, Stephen, Brown, J B, Capuzzi, Stephen J, Chushak, Yaroslav, Ciallella, Heather, Clark, Alex M, Consonni, Viviana, Daga, Pankaj R, Ekins, Sean, Farag, Sherif, Fedorov, Maxim, Fourches, Denis, Gadaleta, Domenico, Gao, Feng, Gearhart, Jeffery M, Goh, Garett, Goodman, Jonathan M, Grisoni, Francesca, Grulke, Christopher M, Hartung, Thomas, Hirn, Matthew, Karpov, Pavel, Korotcov, Alexandru, Lavado, Giovanna J, Lawless, Michael, Li, Xinhao, Luechtefeld, Thomas, Lunghini, Filippo, Mangiatordi, Giuseppe F, Marcou, Gilles, Marsh, Dan, Martin, Todd, Mauri, Andrea, Muratov, Eugene N, Myatt, Glenn J, Nguyen, Dac-Trung, Nicolotti, Orazio, Note, Reine, Pande, Paritosh, Parks, Amanda K, Peryea, Tyler, Polash, Ahsan H, Rallo, Robert, Roncaglioni, Alessandra, Rowlands, Craig, Ruiz, Patricia, Russo, Daniel P, Sayed, Ahmed, Sayre, Risa, Sheils, Timothy, Siegel, Charles, Silva, Arthur C, Simeonov, Anton, Sosnin, Sergey, Southall, Noel, Strickland, Judy, Tang, Yun, Teppen, Brian, Tetko, Igor V, Thomas, Dennis, Tkachenko, Valery, Todeschini, Roberto, Toma, Cosimo, Tripodi, Ignacio, Trisciuzzi, Daniela, Tropsha, Alexander, Varnek, Alexandre, Vukovic, Kristijan, Wang, Zhongyu, Wang, Liguo, Waters, Katrina M, Wedlake, Andrew J, Wijeyesakere, Sanjeeva J, Wilson, Dan, Xiao, Zijun, Yang, Hongbin, Zahoranszky-Kohalmi, Gergely, Zakharov, Alexey V, Zhang, Fagen F, Zhang, Zhen, Zhao, Tongan, Zhu, Hao, Zorn, Kimberley M, Casey, Warren, and Kleinstreuer, Nicole C
- Abstract
Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silica models built using existing data facilitate rapid acute tox- icity predictions without using animals. Objkctivks: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organ- ized an international collaboration to develop in silica models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). Mkthods: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. Results: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in viva results. Discussion: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in viva rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemica
- Published
- 2021
29. Drug Discovery and Development for Kinetoplastid Diseases
- Author
-
Caffrey, Conor R., primary, Steverding, Dietmar, additional, Ferreira, Rafaela S., additional, Oliveira, Renata B., additional, O'Donoghue, Anthony J., additional, Monti, Ludovica, additional, Ballatore, Carlo, additional, Bachovchin, Kelly A., additional, Ferrins, Lori, additional, Pollastri, Michael P., additional, Zorn, Kimberley M., additional, Foil, Daniel H., additional, Clark, Alex M., additional, Mottin, Melina, additional, Andrade, Carolina H., additional, Siqueira‐Neto, Jair L., additional, and Ekins, Sean, additional
- Published
- 2021
- Full Text
- View/download PDF
30. CATMoS: Collaborative Acute Toxicity Modeling Suite
- Author
-
Mansouri, Kamel, primary, Karmaus, Agnes L., additional, Fitzpatrick, Jeremy, additional, Patlewicz, Grace, additional, Pradeep, Prachi, additional, Alberga, Domenico, additional, Alepee, Nathalie, additional, Allen, Timothy E.H., additional, Allen, Dave, additional, Alves, Vinicius M., additional, Andrade, Carolina H., additional, Auernhammer, Tyler R., additional, Ballabio, Davide, additional, Bell, Shannon, additional, Benfenati, Emilio, additional, Bhattacharya, Sudin, additional, Bastos, Joyce V., additional, Boyd, Stephen, additional, Brown, J.B., additional, Capuzzi, Stephen J., additional, Chushak, Yaroslav, additional, Ciallella, Heather, additional, Clark, Alex M., additional, Consonni, Viviana, additional, Daga, Pankaj R., additional, Ekins, Sean, additional, Farag, Sherif, additional, Fedorov, Maxim, additional, Fourches, Denis, additional, Gadaleta, Domenico, additional, Gao, Feng, additional, Gearhart, Jeffery M., additional, Goh, Garett, additional, Goodman, Jonathan M., additional, Grisoni, Francesca, additional, Grulke, Christopher M., additional, Hartung, Thomas, additional, Hirn, Matthew, additional, Karpov, Pavel, additional, Korotcov, Alexandru, additional, Lavado, Giovanna J., additional, Lawless, Michael, additional, Li, Xinhao, additional, Luechtefeld, Thomas, additional, Lunghini, Filippo, additional, Mangiatordi, Giuseppe F., additional, Marcou, Gilles, additional, Marsh, Dan, additional, Martin, Todd, additional, Mauri, Andrea, additional, Muratov, Eugene N., additional, Myatt, Glenn J., additional, Nguyen, Dac-Trung, additional, Nicolotti, Orazio, additional, Note, Reine, additional, Pande, Paritosh, additional, Parks, Amanda K., additional, Peryea, Tyler, additional, Polash, Ahsan H., additional, Rallo, Robert, additional, Roncaglioni, Alessandra, additional, Rowlands, Craig, additional, Ruiz, Patricia, additional, Russo, Daniel P., additional, Sayed, Ahmed, additional, Sayre, Risa, additional, Sheils, Timothy, additional, Siegel, Charles, additional, Silva, Arthur C., additional, Simeonov, Anton, additional, Sosnin, Sergey, additional, Southall, Noel, additional, Strickland, Judy, additional, Tang, Yun, additional, Teppen, Brian, additional, Tetko, Igor V., additional, Thomas, Dennis, additional, Tkachenko, Valery, additional, Todeschini, Roberto, additional, Toma, Cosimo, additional, Tripodi, Ignacio, additional, Trisciuzzi, Daniela, additional, Tropsha, Alexander, additional, Varnek, Alexandre, additional, Vukovic, Kristijan, additional, Wang, Zhongyu, additional, Wang, Liguo, additional, Waters, Katrina M., additional, Wedlake, Andrew J., additional, Wijeyesakere, Sanjeeva J., additional, Wilson, Dan, additional, Xiao, Zijun, additional, Yang, Hongbin, additional, Zahoranszky-Kohalmi, Gergely, additional, Zakharov, Alexey V., additional, Zhang, Fagen F., additional, Zhang, Zhen, additional, Zhao, Tongan, additional, Zhu, Hao, additional, Zorn, Kimberley M., additional, Casey, Warren, additional, and Kleinstreuer, Nicole C., additional
- Published
- 2021
- Full Text
- View/download PDF
31. Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual‐Stage Activity
- Author
-
Lima, Marilia N. N., primary, Borba, Joyce V. B., additional, Cassiano, Gustavo C., additional, Mottin, Melina, additional, Mendonça, Sabrina S., additional, Silva, Arthur C., additional, Tomaz, Kaira C. P., additional, Calit, Juliana, additional, Bargieri, Daniel Y., additional, Costa, Fabio T. M., additional, and Andrade, Carolina H., additional
- Published
- 2021
- Full Text
- View/download PDF
32. Anti-inflammatory effect of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol, a new derivative of 4-nerolidylcatechol
- Author
-
Lino, Roberta Campos, Martins, Fabiula Ines, Florentino, Iziara Ferreira, Nascimento, Marcus Vinicius Mariano, Galdino, Pablinny Moreira, Andrade, Carolina H., Rezende, Kênnia Rocha, Menegatti, Ricardo, and Costa, Elson Alves
- Published
- 2013
- Full Text
- View/download PDF
33. A critical overview of computational approaches employed for COVID-19 drug discovery
- Author
-
Muratov, Eugene N., primary, Amaro, Rommie, additional, Andrade, Carolina H., additional, Brown, Nathan, additional, Ekins, Sean, additional, Fourches, Denis, additional, Isayev, Olexandr, additional, Kozakov, Dima, additional, Medina-Franco, José L., additional, Merz, Kenneth M., additional, Oprea, Tudor I., additional, Poroikov, Vladimir, additional, Schneider, Gisbert, additional, Todd, Matthew H., additional, Varnek, Alexandre, additional, Winkler, David A., additional, Zakharov, Alexey V., additional, Cherkasov, Artem, additional, and Tropsha, Alexander, additional
- Published
- 2021
- Full Text
- View/download PDF
34. List of contributors
- Author
-
Akortia, Eric, Alla, Sai Radha Mani, Alves, Vinicius M., Andrade, Carolina H., Avram, Speranta, Bao, Tong, Benfenati, Emilio, Braga, Rodolpho C., Buiu, Catalin, Chakravarti, Suman K., Chen, Jingwen, Chen, Minjun, Ciura, Krzesimir, Colombo, Erika, Cross, Kevin P., Cui, Shixuan, del Giudice, Giusy, Dong, Fan, Duchowicz, Pablo R., Egbi, Courage, Egodawatta, Prasanna, Elakkiya, Elango, Federico, Antonio, Fratello, Michele, Fu, Zhiqiang, Furuhama, Ayako, Gao, Yuchen, Garro Martinez, Juan C., Gbeddy, Gustav, Giner, Beatriz, Glover, Eric, Goonetilleke, Ashantha, Greco, Dario, Gromelski, Maciej, Gu, Yaxin, Gui, Binxin, Guo, Jing, Guo, Wenjing, He, Jiale, He, Minghui, Hong, Huixiao, Honma, Masamitsu, Huang, Shuheng, Huang, Ruili, Huang, Meiling, Jaeger, Martin, Jillella, Gopala Krishna, Johnson, Candice, Kasamatsu, Toshio, Khan, Pathan Mohsin, Koster, Sander, Kusko, Rebecca, Lee, Myeongsang, Li, Chao, Li, Fei, Li, Bohao, Li, Menglong, Li, Dongying, Li, Jinjie, Li, Xuehua, Li, Zoe, Liao, Tsung-Jen, Liu, Yuan, Liu, Huihui, Liu, Jie, Liu, Wenjia, Lomba, Laura, Lou, Chaofeng, Ma, Guangcai, Manganelli, Serena, Mei, Hu, Mendonca, Sabrina S., Mizuno, Tadahaya, Myatt, Glenn J., Ngan, Deborah K., Ning, Baitang, Pandit, Shraddha, Parthasarathi, Ramakrishnan, Patterson, Tucker A., Pavel, Alisa, Prabhu, Paulraj, Puzyn, Tomasz, Qu, Jiao, Roncaglioni, Alessandra, Roy, Kunal, Saarimäki, Laura Aliisa, Saavedra, Laura M., Sanches, Igor H., Schilter, Benoit, Selvaraj, Chandrabose, Serra, Angela, Shi, Wei, Singh, Prakrity, Singh, Sanjeev Kumar, Sogor, Catalina, Song, Meng, Sosnowska, Anita, Su, Limin, Sugiyama, Kei-ichi, Swirog, Marta, Tang, Yun, Teng, Yuefa, Tong, Weida, Tropsha, Alexander, Udrea, Ana-Maria, Velmurugan, Devadasan, Voigt, Melanie, Wang, Haobo, Wang, Xiaoqing, Wang, Zhongyu, Wang, Xueyu, Wei, Xiaoxuan, Wen, Zhining, Wu, Yiqu, Wyrzykowska, Ewelina, Xiao, Fang, Xie, Hong-Bin, Xu, Tuan, Xu, Liang, Yang, Xianhai, Yu, Haiying, Zhang, Yuxuan, Zhang, Jiachen, Zhao, Jingwen, Zhao, Yuanhui, Zhu, Minghua, Zhuang, Shulin, and Zou, Wen
- Published
- 2023
- Full Text
- View/download PDF
35. Chapter Five - Shortcuts to schistosomiasis drug discovery: The state-of-the-art
- Author
-
Moreira-Filho, José T., Dantas, Rafael F., Senger, Mário R., Silva, Arthur C., Campos, Dulcinea M.B., Muratov, Eugene, Silva-Junior, Floriano P., Andrade, Carolina H., and Neves, Bruno J.
- Published
- 2019
- Full Text
- View/download PDF
36. CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
- Author
-
Mansouri, Kamel, Kleinstreuer, Nicole, Abdelaziz, Ahmed M., Alberga, Domenico, Alves, Vinicius M., Andersson, Patrik L., Andrade, Carolina H., Bai, Fang, Balabin, Ilya, Ballabio, Davide, Benfenati, Emilio, Bhhatarai, Barun, Boyer, Scott, Chen, Jingwen, Consonni, Viviana, Farag, Sherif, Fourches, Denis, García-Sosa, Alfonso T., Gramatica, Paola, Grisoni, Francesca, Grulke, Chris M., Hong, Huixiao, Horvath, Dragos, Hu, Xin, Huang, Ruili, Jeliazkova, Nina, Li, Jiazhong, Li, Xuehua, Liu, Huanxiang, Manganelli, Serena, Mangiatordi, Giuseppe F., Maran, Uko, Marcou, Gilles, Martin, Todd, Muratov, Eugene, Nguyen, Dac-Trung, Nicolotti, Orazio, Nikolov, Nikolai G., Norinder, Ulf, Papa, Ester, Petitjean, Michel, Pür, Geven, Pogodin, Pavel, Poroikov, Vladimir, Qiao, Xianliang, Richard, Ann M., Roncaglioni, Alessandra, Ruiz, Patricia, Rupakheti, Chetan, Sakkiah, Sugunadevi, Sangion, Alessandro, Schramm, Karl-Werner, Selvaraj, Chandrabose, Shah, Imran, Sild, Sulev, Sun, Lixia, Taboureau, Olivier, Tang, Yun, Tetko, Igor V., Todeschini, Roberto, Tong, Weida, Trisciuzzi, Daniela, Tropsha, Alexander, Van Den Driessche, George, Varnek, Alexandre, Wang, Zhongyu, Wedebye, Eva B., Williams, Antony J., Xie, Hongbin, Zakharov, Alexey V., Zheng, Ziye, Judson, Richard S., Mansouri, Kamel, Kleinstreuer, Nicole, Abdelaziz, Ahmed M., Alberga, Domenico, Alves, Vinicius M., Andersson, Patrik L., Andrade, Carolina H., Bai, Fang, Balabin, Ilya, Ballabio, Davide, Benfenati, Emilio, Bhhatarai, Barun, Boyer, Scott, Chen, Jingwen, Consonni, Viviana, Farag, Sherif, Fourches, Denis, García-Sosa, Alfonso T., Gramatica, Paola, Grisoni, Francesca, Grulke, Chris M., Hong, Huixiao, Horvath, Dragos, Hu, Xin, Huang, Ruili, Jeliazkova, Nina, Li, Jiazhong, Li, Xuehua, Liu, Huanxiang, Manganelli, Serena, Mangiatordi, Giuseppe F., Maran, Uko, Marcou, Gilles, Martin, Todd, Muratov, Eugene, Nguyen, Dac-Trung, Nicolotti, Orazio, Nikolov, Nikolai G., Norinder, Ulf, Papa, Ester, Petitjean, Michel, Pür, Geven, Pogodin, Pavel, Poroikov, Vladimir, Qiao, Xianliang, Richard, Ann M., Roncaglioni, Alessandra, Ruiz, Patricia, Rupakheti, Chetan, Sakkiah, Sugunadevi, Sangion, Alessandro, Schramm, Karl-Werner, Selvaraj, Chandrabose, Shah, Imran, Sild, Sulev, Sun, Lixia, Taboureau, Olivier, Tang, Yun, Tetko, Igor V., Todeschini, Roberto, Tong, Weida, Trisciuzzi, Daniela, Tropsha, Alexander, Van Den Driessche, George, Varnek, Alexandre, Wang, Zhongyu, Wedebye, Eva B., Williams, Antony J., Xie, Hongbin, Zakharov, Alexey V., Zheng, Ziye, and Judson, Richard S.
- Abstract
BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accura
- Published
- 2020
- Full Text
- View/download PDF
37. CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity
- Author
-
Mansouri, K, Kleinstreuer, N, Abdelaziz, A, Alberga, D, Alves, V, Andersson, P, Andrade, C, Bai, F, Balabin, I, Ballabio, D, Benfenati, E, Bhhatarai, B, Boyer, S, Chen, J, Consonni, V, Farag, S, Fourches, D, García-Sosa, A, Gramatica, P, Grisoni, F, Grulke, C, Hong, H, Horvath, D, Hu, X, Huang, R, Jeliazkova, N, Li, J, Li, X, Liu, H, Manganelli, S, Mangiatordi, G, Maran, U, Marcou, G, Martin, T, Muratov, E, Nguyen, D, Nicolotti, O, Nikolov, N, Norinder, U, Papa, E, Petitjean, M, Piir, G, Pogodin, P, Poroikov, V, Qiao, X, Richard, A, Roncaglioni, A, Ruiz, P, Rupakheti, C, Sakkiah, S, Sangion, A, Schramm, K, Selvaraj, C, Shah, I, Sild, S, Sun, L, Taboureau, O, Tang, Y, Tetko, I, Todeschini, R, Tong, W, Trisciuzzi, D, Tropsha, A, Van Den Driessche, G, Varnek, A, Wang, Z, Wedebye, E, Williams, A, Xie, H, Zakharov, A, Zheng, Z, Judson, R, Mansouri, Kamel, Kleinstreuer, Nicole, Abdelaziz, Ahmed M., Alberga, Domenico, Alves, Vinicius M., Andersson, Patrik L., Andrade, Carolina H., Bai, Fang, Balabin, Ilya, Ballabio, Davide, Benfenati, Emilio, Bhhatarai, Barun, Boyer, Scott, Chen, Jingwen, Consonni, Viviana, Farag, Sherif, Fourches, Denis, García-Sosa, Alfonso T., Gramatica, Paola, Grisoni, Francesca, Grulke, Chris M., Hong, Huixiao, Horvath, Dragos, Hu, Xin, Huang, Ruili, Jeliazkova, Nina, Li, Jiazhong, Li, Xuehua, Liu, Huanxiang, Manganelli, Serena, Mangiatordi, Giuseppe F., Maran, Uko, Marcou, Gilles, Martin, Todd, Muratov, Eugene, Nguyen, Dac-Trung, Nicolotti, Orazio, Nikolov, Nikolai G., Norinder, Ulf, Papa, Ester, Petitjean, Michel, Piir, Geven, Pogodin, Pavel, Poroikov, Vladimir, Qiao, Xianliang, Richard, Ann M., Roncaglioni, Alessandra, Ruiz, Patricia, Rupakheti, Chetan, Sakkiah, Sugunadevi, Sangion, Alessandro, Schramm, Karl-Werner, Selvaraj, Chandrabose, Shah, Imran, Sild, Sulev, Sun, Lixia, Taboureau, Olivier, Tang, Yun, Tetko, Igor V., Todeschini, Roberto, Tong, Weida, Trisciuzzi, Daniela, Tropsha, Alexander, Van Den Driessche, George, Varnek, Alexandre, Wang, Zhongyu, Wedebye, Eva B., Williams, Antony J., Xie, Hongbin, Zakharov, Alexey V., Zheng, Ziye, Judson, Richard S., Mansouri, K, Kleinstreuer, N, Abdelaziz, A, Alberga, D, Alves, V, Andersson, P, Andrade, C, Bai, F, Balabin, I, Ballabio, D, Benfenati, E, Bhhatarai, B, Boyer, S, Chen, J, Consonni, V, Farag, S, Fourches, D, García-Sosa, A, Gramatica, P, Grisoni, F, Grulke, C, Hong, H, Horvath, D, Hu, X, Huang, R, Jeliazkova, N, Li, J, Li, X, Liu, H, Manganelli, S, Mangiatordi, G, Maran, U, Marcou, G, Martin, T, Muratov, E, Nguyen, D, Nicolotti, O, Nikolov, N, Norinder, U, Papa, E, Petitjean, M, Piir, G, Pogodin, P, Poroikov, V, Qiao, X, Richard, A, Roncaglioni, A, Ruiz, P, Rupakheti, C, Sakkiah, S, Sangion, A, Schramm, K, Selvaraj, C, Shah, I, Sild, S, Sun, L, Taboureau, O, Tang, Y, Tetko, I, Todeschini, R, Tong, W, Trisciuzzi, D, Tropsha, A, Van Den Driessche, G, Varnek, A, Wang, Z, Wedebye, E, Williams, A, Xie, H, Zakharov, A, Zheng, Z, Judson, R, Mansouri, Kamel, Kleinstreuer, Nicole, Abdelaziz, Ahmed M., Alberga, Domenico, Alves, Vinicius M., Andersson, Patrik L., Andrade, Carolina H., Bai, Fang, Balabin, Ilya, Ballabio, Davide, Benfenati, Emilio, Bhhatarai, Barun, Boyer, Scott, Chen, Jingwen, Consonni, Viviana, Farag, Sherif, Fourches, Denis, García-Sosa, Alfonso T., Gramatica, Paola, Grisoni, Francesca, Grulke, Chris M., Hong, Huixiao, Horvath, Dragos, Hu, Xin, Huang, Ruili, Jeliazkova, Nina, Li, Jiazhong, Li, Xuehua, Liu, Huanxiang, Manganelli, Serena, Mangiatordi, Giuseppe F., Maran, Uko, Marcou, Gilles, Martin, Todd, Muratov, Eugene, Nguyen, Dac-Trung, Nicolotti, Orazio, Nikolov, Nikolai G., Norinder, Ulf, Papa, Ester, Petitjean, Michel, Piir, Geven, Pogodin, Pavel, Poroikov, Vladimir, Qiao, Xianliang, Richard, Ann M., Roncaglioni, Alessandra, Ruiz, Patricia, Rupakheti, Chetan, Sakkiah, Sugunadevi, Sangion, Alessandro, Schramm, Karl-Werner, Selvaraj, Chandrabose, Shah, Imran, Sild, Sulev, Sun, Lixia, Taboureau, Olivier, Tang, Yun, Tetko, Igor V., Todeschini, Roberto, Tong, Weida, Trisciuzzi, Daniela, Tropsha, Alexander, Van Den Driessche, George, Varnek, Alexandre, Wang, Zhongyu, Wedebye, Eva B., Williams, Antony J., Xie, Hongbin, Zakharov, Alexey V., Zheng, Ziye, and Judson, Richard S.
- Abstract
BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP’s list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCastTM metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCastTM/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy ass
- Published
- 2020
38. CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity
- Author
-
Mansouri, Kamel, primary, Kleinstreuer, Nicole, additional, Abdelaziz, Ahmed M., additional, Alberga, Domenico, additional, Alves, Vinicius M., additional, Andersson, Patrik L., additional, Andrade, Carolina H., additional, Bai, Fang, additional, Balabin, Ilya, additional, Ballabio, Davide, additional, Benfenati, Emilio, additional, Bhhatarai, Barun, additional, Boyer, Scott, additional, Chen, Jingwen, additional, Consonni, Viviana, additional, Farag, Sherif, additional, Fourches, Denis, additional, García-Sosa, Alfonso T., additional, Gramatica, Paola, additional, Grisoni, Francesca, additional, Grulke, Chris M., additional, Hong, Huixiao, additional, Horvath, Dragos, additional, Hu, Xin, additional, Huang, Ruili, additional, Jeliazkova, Nina, additional, Li, Jiazhong, additional, Li, Xuehua, additional, Liu, Huanxiang, additional, Manganelli, Serena, additional, Mangiatordi, Giuseppe F., additional, Maran, Uko, additional, Marcou, Gilles, additional, Martin, Todd, additional, Muratov, Eugene, additional, Nguyen, Dac-Trung, additional, Nicolotti, Orazio, additional, Nikolov, Nikolai G., additional, Norinder, Ulf, additional, Papa, Ester, additional, Petitjean, Michel, additional, Piir, Geven, additional, Pogodin, Pavel, additional, Poroikov, Vladimir, additional, Qiao, Xianliang, additional, Richard, Ann M., additional, Roncaglioni, Alessandra, additional, Ruiz, Patricia, additional, Rupakheti, Chetan, additional, Sakkiah, Sugunadevi, additional, Sangion, Alessandro, additional, Schramm, Karl-Werner, additional, Selvaraj, Chandrabose, additional, Shah, Imran, additional, Sild, Sulev, additional, Sun, Lixia, additional, Taboureau, Olivier, additional, Tang, Yun, additional, Tetko, Igor V., additional, Todeschini, Roberto, additional, Tong, Weida, additional, Trisciuzzi, Daniela, additional, Tropsha, Alexander, additional, Van Den Driessche, George, additional, Varnek, Alexandre, additional, Wang, Zhongyu, additional, Wedebye, Eva B., additional, Williams, Antony J., additional, Xie, Hongbin, additional, Zakharov, Alexey V., additional, Zheng, Ziye, additional, and Judson, Richard S., additional
- Published
- 2020
- Full Text
- View/download PDF
39. Development of Web and Mobile Applications for Chemical Toxicity Prediction
- Author
-
Alves, Vinicius M., Braga, Rodolpho C., Muratov, Eugene, and Andrade, Carolina H.
- Subjects
toxicity prediction ,QSAR ,Pred-hERG ,Pred-Skin ,web app ,mobile - Abstract
Computational tools are recognized to provide high-quality predictions for the assessment of chemical toxicity. In the recent years, mobile devices have become ubiquitous, allowing for the development of innovative and useful models implemented as chemical software applications. Here, we will briefly discuss this recent uptick in the development of web-based and mobile applications for chemical problems, focusing on best practices, development, usage and interpretation. As an example, we also describe two innovative apps (Pred-hERG and Pred-Skin) for chemical toxicity prediction developed in our laboratory. These applications are based on predictive quantitative structure-activity relationships (QSAR) models developed using the largest publicly available datasets of structurally diverse compounds. The developed tools ensure both highly accurate predictions and easy interpretation of the models, allowing users to discriminate potential toxicants and to purpose structural modifications to design safer chemicals.
- Published
- 2018
40. Cheminformatics-driven discovery of polymeric micelle formulations for poorly soluble drugs
- Author
-
Alves, Vinicius M., primary, Hwang, Duhyeong, additional, Muratov, Eugene, additional, Sokolsky-Papkov, Marina, additional, Varlamova, Ekaterina, additional, Vinod, Natasha, additional, Lim, Chaemin, additional, Andrade, Carolina H., additional, Tropsha, Alexander, additional, and Kabanov, Alexander, additional
- Published
- 2019
- Full Text
- View/download PDF
41. Antitrypanosomal Activity of Acetogenins Isolated from the Seeds of Porcelia macrocarpa Is Associated with Alterations in Both Plasma Membrane Electric Potential and Mitochondrial Membrane Potential
- Author
-
Oliveira, Emerson A., primary, Brito, Ivanildo A., additional, Lima, Marta L., additional, Romanelli, Maiara, additional, Moreira-Filho, José T., additional, Neves, Bruno J., additional, Andrade, Carolina H., additional, Sartorelli, Patricia, additional, Tempone, Andre G., additional, Costa-Silva, Thais A., additional, and Lago, João Henrique G., additional
- Published
- 2019
- Full Text
- View/download PDF
42. promising starting points for drug design
- Author
-
Gomes, Marcelo N., Muratov, Eugene N., Pereira, Maristela, Peixoto, Josana C., Rosseto, Lucimar P., Cravo, Pedro V.L., Andrade, Carolina H., Neves, Bruno J., Instituto de Higiene e Medicina Tropical (IHMT), Global Health and Tropical Medicine (GHTM), and Vector borne diseases and pathogens (VBD)
- Subjects
Natural products ,Chalcone derivatives ,SDG 3 - Good Health and Well-being ,Molecular modification strategies ,Organic Chemistry ,Drug Discovery ,Chalcone synthesis ,Computer-assisted drug design - Abstract
Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations. publishersversion published
- Published
- 2017
43. Oy Vey! A Comment on “Machine Learning of Toxicological Big Data Enables Read-Across Structure Activity Relationships Outperforming Animal Test Reproducibility”
- Author
-
Alves, Vinicius M, primary, Borba, Joyce, additional, Capuzzi, Stephen J, additional, Muratov, Eugene, additional, Andrade, Carolina H, additional, Rusyn, Ivan, additional, and Tropsha, Alexander, additional
- Published
- 2018
- Full Text
- View/download PDF
44. Computer-aided identification of novel anti-paracoccidioidomycosis compounds
- Author
-
Silva, Lívia C, primary, Neves, Bruno J, additional, Gomes, Marcelo N, additional, Melo-Filho, Cleber C, additional, Soares, Célia MA, additional, Andrade, Carolina H, additional, and Pereira, Maristela, additional
- Published
- 2018
- Full Text
- View/download PDF
45. QSAR-Driven Design and Discovery of Novel Compounds With Antiplasmodial and Transmission Blocking Activities
- Author
-
Lima, Marilia N. N., primary, Melo-Filho, Cleber C., additional, Cassiano, Gustavo C., additional, Neves, Bruno J., additional, Alves, Vinicius M., additional, Braga, Rodolpho C., additional, Cravo, Pedro V. L., additional, Muratov, Eugene N., additional, Calit, Juliana, additional, Bargieri, Daniel Y., additional, Costa, Fabio T. M., additional, and Andrade, Carolina H., additional
- Published
- 2018
- Full Text
- View/download PDF
46. QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni
- Author
-
Melo-Filho, Cleber C, Dantas, Rafael F, Braga, Rodolpho C, Neves, Bruno J, Senger, Mario R, Valente, Walter CG, Rezende-Neto, João M, Chaves, Willian T, Muratov, Eugene N, Paveley, Ross A, Furnham, Nicholas, Kamentsky, Lee, Carpenter, Anne E, Silva-Junior, Floriano P, and Andrade, Carolina H
- Abstract
Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents.
- Published
- 2016
47. In Vitro , In Silico , and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi
- Author
-
Santos, Camila C., primary, Lionel, Jéssica R., additional, Peres, Raiza B., additional, Batista, Marcos M., additional, da Silva, Patrícia B., additional, de Oliveira, Gabriel M., additional, da Silva, Cristiane F., additional, Batista, Denise G. J., additional, Souza, Sandra Maria O., additional, Andrade, Carolina H., additional, Neves, Bruno J., additional, Braga, Rodolpho C., additional, Patrick, Donald A., additional, Bakunova, Svetlana M., additional, Tidwell, Richard R., additional, and Soeiro, Maria de Nazaré C., additional
- Published
- 2018
- Full Text
- View/download PDF
48. Open Drug Discovery for Zika Virus
- Author
-
Ekins, Sean, Mietchen, Daniel, Coffee, Megan, Stratton, Thomas P., Freundlich, Joel S., Freitas-Junior, Lucio H., Muratov, Eugene, Siqueira-Neto, Jair L., Williams, Antony J., and Andrade, Carolina H.
- Abstract
A preprint submitted Opinion article - See also supplemental dataSee updated version
- Published
- 2016
- Full Text
- View/download PDF
49. Supplemental Data.docx
- Author
-
Ekins, Sean, Mietchen, Daniel, Coffee, Megan, Stratton, Thomas P., Freundlich, Joel S., Freitas-Junior, Lucio H., Muratov, Eugene, Siqueira-Neto, Jair L., Williams, Antony J., and Andrade, Carolina H.
- Subjects
viruses - Abstract
Supplemental data to preprint Open Drug Discovery for the Zika Virus
- Published
- 2016
- Full Text
- View/download PDF
50. New draft item
- Author
-
Ekins, Sean, Mietchen, Daniel, Coffee, Megan, Stratton, Thomas P., Freundlich, Joel S., Freitas-Junior, Lucio H., Muratov, Eugene, Siqueira-Neto, Jair L., Williams, Antony J., and Andrade, Carolina H.
- Abstract
A preprint submitted Opinion article - See also supplemental data
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.