Searching potential antiviral candidates for the treatment of the 2019 novel coronavirus based on DFT calculations and molecular docking

Abstract

In the present work, the succinic acid (SA), L-pyroglutamic acid (L-PGA), N-phenyl-thioacetamide (N-NPTA), 2-amino-5-chloropyridine hydrogen succinate (ACPS), epigallocatechine Gallate (EGCG) or KDH and, selenomethionine (SeM) compounds have been proposed as potential antiviral candidates to treatment of COVID-19 based on B3LYP/6-311++G∗∗ calculations and molecular docking. Solvation energies, stabilization energies, topological properties have been evaluated as function of acceptors and donors groups present in their structures. ACPS presents the higher reactivity in solution possibly because has the higher nucleophilicity and elecrophilicity indexes while KDH evidence the higher solvation energy probably due to the higher quantity of donors and acceptors groups. NBO studies show that KDH is the most stable in solution. Mapped MEP surfaces have evidenced stronger nucleophilic and electrophilic sites in ACPS, in agreement with the three C=O and two N–H and O–H groups present in this species while KDH has only a C=O group but a total of 19 acceptors and donors groups. From the above studies for six species we can propose that the better potential antiviral candidate to treatment of COVID-19 is ACPS and then, KDH. For a better prediction of the antiviral and anti-inflammatory properties of the proposed compounds, molecular docking calculations were performed by using four structures of COVID-19. Docking results were discussed basing on binding affinities and the interaction types among ligands and different amino acid residues, indicating the powerful ability of KDH and then ACPS ligands on front of the novel coronavirus disease especially for the first and the fourth species (6LU7, 7BTF).

EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro

“…EGCG is reported to inhibit SARS-CoV-2 3CL-protease using purified SARS-CoV-2 3CL-protease protein [ 7 ]. A computer simulation study also supports that EGCG can block the 3CL-protease activity of SARS-CoV-2 [ [8] , [9] , [10] , [11] ]. In addition, statistical analysis demonstrated that the countries with high green tea consumption showed a striking reduction of COVID-19 risk including morbidity and mortality [ 12 ].…”

Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study

“…The computational approach has been extensively explored in studies of possible drugs against infection by SARS-CoV-2. Sagaama et al [ 27 ] presented results of possible drugs complexed with SARS-CoV-2 proteins using theoretical level DFT and Molecular Docking as well as Jordaan et al [ 28 ] with results involving Simvastatin, Lovastatin, Oxacilin, podophyllotoxin, gefitinib with SARS-CoV-2 main protease. As a consequence, the main goal of this article is to present the result of the study of an interaction between ( R and S )-Linezolid with RBD of SARS-CoV-2 spike protein in complex with human ACE2.…”

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

“…DFT-based optimized geometry allows for the study of frontier molecular orbitals that play an important role in understanding the interaction mechanisms between drugs and their receptors in determining the hit ligands against SARS-CoV-2 [86][87][88][89][90]. The difference between HOMO (highest-energy molecular orbital occupied by electrons) and LUMO (lowest-energy molecular orbital not occupied by electrons) energy values plays a critical role in determining the chemical reactivity, charge transfer capabilities, and bioactivity potential of molecular systems [91][92][93][94][95]. The ligand with a narrower HOMO-LUMO energy gap will also have a higher potential to inhibit the active site of the protein [96,97].…”