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

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

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.