Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box’s Molecules

Cleidy Osorio Mogolón, Gustavo E.Olivos Ramírez, Kewin Otazu, Manuel E. Chenet-Zuta, Georcki Ropón Palacios, Cinthia Das Dores Aguiar, Ihosvany Camps, Gabriel M. Jimenez-Avalos, Eduardo Apari-Cossio, Natalia E. Torres Moreira, Reyna G. Cárdenas-Cárdenas

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The world is currently facing a pandemic initiated by the new coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. Viral transcription and replication are the fundamental processes of any virus. They alow the synthesis of genetic material and the consequent multiplication of the virus to infect other Cells or organisms. Methods: The most important protein in SARS-CoV-2 is the RNA polymerase (RdRp or nsp12), responsible for both processes. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for a drug search, like virtual screening and molecular docking. Here, the Pathogen Box database of chemical compounds was used together with Remdesivir, Beclabuvir, and Sofosbuvir drugs as potential inhibitors of nsp12. Results: The results showed Top10 potential target inhibitors with binding energy (∆G) higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with ∆G = −7.53 kcal/mol, present interactions with three important residues of the nsp12 catalytic site. Conclusion: These proposed ligands would be used for subsequent validation by molecular dynamics, where they can be considered as drugs for the development of effective treatments against this new pandemic.

Original languageEnglish
Pages (from-to)808-820
Number of pages13
JournalLetters in Drug Design and Discovery
Volume20
Issue number7
DOIs
StatePublished - 2023

Keywords

  • RNA polymerase
  • SARS-CoV-2
  • drug repurposing
  • molecular docking
  • nsp12
  • pandemic

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