The world is currently facing a pandemic caused by the new 2019 coronavirus disease (COVID-19), caused by SARS-CoV-2. Among the fundamental processes of this virus are viral transcription and replication. They allow the synthesis<br>of genetic material and the consequent multiplication of the virus to infect other cells or organisms. These are performed by a multi-subunit machinery of various nonstructural proteins (nsp); among which the RNA-dependent RNA<br>polymerase (RdRp or nsp12) is the most important, and, at the same time, conserved among coronaviruses. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for drug<br>search, like virtual screening and molecular docking. The region considered for virtual screening has three important amino acids for protein catalysis: T680 (located in Motif A), N691 and D623 (located in Motif B), where a grid box was located. In turn, applying the concept of drug repositioning is<br>considered as a quick response in the treatment of sudden outbreaks of diseases. Here, we used the Pathogen Box, a database of chemical compounds analyzed for the treatment against malaria, which were filtered under the criteria of selecting those that do not present any violation of Lipinski's<br>Rule of Five. At the same time, the Remdesivir, Beclabuvir and Sofosbuvir drug, previously used in <i>in silico</i> and clinical studies for inhibition of nsp12, were used as positive controls. The results showed a Top10 potential target inhibitors, with binding energy higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with -7.53 kcal/mol, present interactions with the three important residues of the nsp12 catalytic site. These proposed ligands would be used for subsequent validation by molecular dynamics, where they can be<br>considered as drugs for the development of effective treatments against this new pandemic.
Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach
