Luana N.O. Leal da Cunha, Tiago Tizziani, Gabriella B. Souza, Monalisa A. Moreira, José S.S. Neto, Carlos V.D. dos Santos, Maryelle G. de Carvalho, Eduardo M. Dalmarco, Leonardo B. Turqueti, Marcus Tullius Scotti, Luciana Scotti, Francisco F. de Assis, Antonio Luiz Braga and Louis Pergaud Sandjo* Pages 2530 - 2564 ( 35 )
Background: COVID-19 is still causing long-term health consequences, mass deaths, and collapsing healthcare systems around the world. There are no efficient drugs for its treatment. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CLpro) and papain-like protease (PLpro) sequences, respectively. This resemblance could be important in the search for drug candidates with antiviral effects against SARS-CoV-2.
Objective: This paper is a compilation of natural products that inhibit SARS-CoV 3CLpro and PLpro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CLpro and PLpro as targets to propose a list of hit compounds.
Methods: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages.
Results: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed immunomodulatory effects in previous studies. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PLpro and 3CLpro, respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature.
Conclusion: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidates for the search of antibiotics against COVID-19.
Natural products, COVID-19, 3CL<sup>pro</sup> and PL<sup>pro</sup> inhibitory effect, anti-inflammatory effect, immunomodulatory effect, drug discovery.
Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Farmácia, CCS, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Program in Natural and Synthetic Bioactive Products Federal University of Paraíba Cidade Universitária-Castelo Branco III, João Pessoa, PB, Program in Natural and Synthetic Bioactive Products Federal University of Paraíba Cidade Universitária-Castelo Branco III, João Pessoa, PB, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Química, CFM, Department of Chemistry, Universidade Federal de Santa Catarina, Florianópolis