Evaluation of drug repositioning by molecular docking of pharmaceutical resources available in the Brazilian healthcare system against SARS-CoV-2

Matheus V C Grahl; Allan M Alcará; Ana Paula A Perin; Carlo F Moro; Éderson S M Pinto; Bruno C Feltes; Isadora M Ghilardi; Felipe V F Rodrigues; Marcio Dorn; Jaderson C da Costa; Osmar Norberto de Souza; Rodrigo Ligabue-Braun

doi:10.1016/j.imu.2021.100539

Evaluation of drug repositioning by molecular docking of pharmaceutical resources available in the Brazilian healthcare system against SARS-CoV-2

Inform Med Unlocked. 2021:23:100539. doi: 10.1016/j.imu.2021.100539. Epub 2021 Feb 19.

Authors

Matheus V C Grahl^{1

2}, Allan M Alcará^{1

3}, Ana Paula A Perin⁴, Carlo F Moro^{1

2}, Éderson S M Pinto^{4

5}, Bruno C Feltes^{5

6}, Isadora M Ghilardi^{1

3}, Felipe V F Rodrigues^{1

3}, Marcio Dorn⁵, Jaderson C da Costa^{1

2

3}, Osmar Norberto de Souza⁷, Rodrigo Ligabue-Braun⁸

Affiliations

¹ Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
² Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
³ Graduate Program in Medicine, Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
⁴ Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, RS, Brazil.
⁵ Laboratory of Structural Bioinformatics and Computational Biology, Institute of Informatics, Federal University of Rio Grande do Sul, RS, Brazil.
⁶ Laboratory of Immunobiology and Immunogenetics, Institute of Biosciences, Federal University of Rio Grande do Sul, RS, Brazil.
⁷ School of Technology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
⁸ Department of Pharmacosciences and Graduate Program in Biosciences (PPGBio), Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil.

Abstract

In 2020 SARS-CoV-2 reached pandemic status, reaching Brazil in mid-February. As of now, no specific drugs for treating the disease are available. In this work, the possibility of interaction between SARS-CoV-2 viral proteins (open and closed spike protein, isolate spike protein RBD, NSP 10, NSP 16, main protease, and RdRp polymerase) and multiple molecules is addressed through the repositioning of drugs available for the treatment of other diseases that are approved by the FDA and covered by SUS, the Brazilian Public Health System. Three different docking software were used, followed by a unification of the results by independent evaluation. Afterwards, the chemical interactions of the compounds with the targets were inspected via molecular dynamics and analyzed. The results point to a potential effectiveness of Penciclovir, Ribavirin, and Zanamivir, from a set of 48 potential candidates. They may also be multi-target drugs, showing high affinity with more than one viral protein. Further in vitro and in vivo validation is required to assess the suitability of repositioning the proposed drugs for COVID-19.

Keywords: COVID19; Drug repositioning; Molecular docking; SARS-CoV-2; SUS.