Tags

Type your tag names separated by a space and hit enter

Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19.
Life Sci. 2020 Jun 11; 256:117963.LS

Abstract

The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed to subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.

Authors+Show Affiliations

Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil. Electronic address: lorane@unifap.br.Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil.Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil.Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil.Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil.Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Chemistry, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Chemistry, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Chemistry, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32535080

Citation

Hage-Melim, Lorane Izabel da Silva, et al. "Virtual Screening, ADME/Tox Predictions and the Drug Repurposing Concept for Future Use of Old Drugs Against the COVID-19." Life Sciences, vol. 256, 2020, p. 117963.
Hage-Melim LIDS, Federico LB, de Oliveira NKS, et al. Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19. Life Sci. 2020;256:117963.
Hage-Melim, L. I. D. S., Federico, L. B., de Oliveira, N. K. S., Francisco, V. C. C., Correia, L. C., de Lima, H. B., Gomes, S. Q., Barcelos, M. P., Francischini, I. A. G., & da Silva, C. H. T. P. (2020). Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19. Life Sciences, 256, 117963. https://doi.org/10.1016/j.lfs.2020.117963
Hage-Melim LIDS, et al. Virtual Screening, ADME/Tox Predictions and the Drug Repurposing Concept for Future Use of Old Drugs Against the COVID-19. Life Sci. 2020 Jun 11;256:117963. PubMed PMID: 32535080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19. AU - Hage-Melim,Lorane Izabel da Silva, AU - Federico,Leonardo Bruno, AU - de Oliveira,Nayana Keyla Seabra, AU - Francisco,Viviane Cristina Cardoso, AU - Correia,Lenir Cabral, AU - de Lima,Henrique Barros, AU - Gomes,Suzane Quintana, AU - Barcelos,Mariana Pegrucci, AU - Francischini,Isaque Antônio Galindo, AU - da Silva,Carlos Henrique Tomich de Paula, Y1 - 2020/06/11/ PY - 2020/04/14/received PY - 2020/06/02/revised PY - 2020/06/09/accepted PY - 2020/6/15/pubmed PY - 2020/6/15/medline PY - 2020/6/15/entrez KW - Computational drug repurposing KW - Coronavirus KW - SARS-CoV-2 SP - 117963 EP - 117963 JF - Life sciences JO - Life Sci. VL - 256 N2 - The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed to subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32535080/Virtual_screening,_ADME/Tox_predictions_and_the_drug_repurposing_concept_for_future_use_of_old_drugs_against_the_COVID-19 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30713-X DB - PRIME DP - Unbound Medicine ER -