Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening

Autor(es)

de Oliveira, Osmair Vital ^[1] ; Rocha, Gerd B. ^[2] ; Paluch, Andrew S. ^[3] ; Costa, Luciano T. ^[4]

Afiliação do(s) autor(es)

^[1] Inst Fed Educ Ciencia & Tecnol Sao Paulo, Campus Catanduva, BR-15808305 Catanduva, SP - Brazil

^[2] Univ Fed Paraiba, Dept Quim, Joao Pessoa, Paraiba - Brazil

^[3] Miami Univ, Dept Chem Paper & Biomed Engn, Oxford, OH 45056 - USA

^[4] Univ Fed Fluminense Outeiro Sao Joao Batista, Inst Quim, MolMod CS, Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; v. 39, n. 11, p. 3924-3933, JUL 24 2021.
• Citações Web of Science: 39

Resumo

Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from ``up{''} to ``down{''} conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replicationin vitro.MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak. (AU)

• Processo FAPESP: 18/19844-8 - Estudo Molecular do Encapsulamento de Compostos Bioativos na Cucurbit[7]urila
• Beneficiário: Osmair Vital de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular