Computational screening for potential drug candidates against the SARS-CoV-2 main protease [version 2; peer review: 2 approved]
Bruno Silva Andrade,
Preetam Ghosh,
Debmalya Barh,
Sandeep Tiwari,
Raner José Santana Silva,
Wagner Rodrigues de Assis Soares,
Tarcisio Silva Melo,
Andria Santos Freitas,
Patrícia González-Grande,
Lucas Sousa Palmeira,
Luiz Carlos Junior Alcantara,
Marta Giovanetti,
Aristóteles Góes-Neto,
Vasco Ariston de Carvalho Azevedo
Affiliations
Bruno Silva Andrade
Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, 45205-490, Brazil
Preetam Ghosh
Department of Computer Science, Virginia Commonwealth University, Richmond, VA, 23284, USA
Debmalya Barh
Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, India
Sandeep Tiwari
Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, MG, Brazil
Raner José Santana Silva
Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil
Wagner Rodrigues de Assis Soares
Departamento de Saúde II, Universidade Estadual do Sudoeste da Bahia., Jequié, BA, Brazil
Tarcisio Silva Melo
Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, 45205-490, Brazil
Andria Santos Freitas
Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil
Patrícia González-Grande
Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil
Lucas Sousa Palmeira
Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, 45205-490, Brazil
Luiz Carlos Junior Alcantara
Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
Marta Giovanetti
Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
Aristóteles Góes-Neto
Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
Vasco Ariston de Carvalho Azevedo
Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, MG, Brazil
Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.
