Dataset Information

Inhibitory efficacy of 2, 4-diacetylphloroglucinol against SARS-COV-2 proteins: in silico study

ABSTRACT: The pandemic of Severe Acute Respiratory Syndrome Coronavirus-2 has affected millions of people worldwide with common symptoms of fever, cough, and respiratory complications. The pandemic has posed a huge challenge to emergency health services due to unavailability of potent therapeutic drugs. The proteins associated with the viral pathogenesis has been identified as suitable targets for drug design and warrants effective drug discovery to abate COVID-19. The papain-like protease (PLpro), nucleocapsid (N), main protease (Mpro) and non-structural protein (nsp12) of SARS-CoV-2, key component of processing of viral polyproteins, transcription, assembly and replication. On this streak, present study evaluated the interaction of ligand 2,4-diacetylphloroglucinol (DAPG) with viral proteins using molecular docking with (i) AutoDock 4.2.6 and (ii) AutoDock Vina followed by molecular dynamic simulation studies of protein-ligand complex configuration. The analysis revealed that PLpro (3E9S) and N (4J3K) protein corresponds to the highest docking score and therefore, selected for molecular dynamics simulation study (100 ns). The study comprised analysis of parameters: (i) RMSD and RMSF, (ii) radius of gyration- which indicated interaction of protein entities with ligand supported steadiness of the complex, (iii) Coulombic and Lennard–Jones interactions, which played a significant role in complex stability. DAPG showed a good number of H-bonds with PLpro and MM-PBSA binding energy when compared to the N protein. This study showed DAPG as a potential bioactive molecule to act as an inhibitor for the PLpro thereby, DAPG can be used as potential inhibitor against SARS-CoV-2 and is potential drug candidate against COVID-19.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11756-021-00979-4.

SUBMITTER: Kankariya R

PROVIDER: S-EPMC8800849 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The current crisis of the COVID-19 pandemic around the world has been devastating as many lives have been lost to the novel SARS CoV-2 virus. Thus, there is an urgent need for the right therapeutic drug to curb the disease. However, there is time constraint in drug development, hence the need for drug repurposing approach, a relatively fast and less expensive alternative. In this study, 1,100 Food and Drug Administration (FDA) approved drugs were obtained from DrugBank and trimmed to 791 ligands based on illicitness, withdrawal from the market, being chemical agents rather than drugs, being investigational drugs and having molecular weight greater than 500 (Kg/mol). The ligands were docked against six drug targets of the novel SARS CoV-2 - 3-chymotrypsin-like protease (3CLpro), Angiotensin-converting enzyme (ACE2), ADP ribose phosphatase of NSP3 (NSP3), NSP9 RNA binding protein (NSP9), RNA dependent RNA polymerase (RdRp) and Replicase Polyprotein 1a (RP1a). UCSF Chimera, PyRx and Discovery Studio, were used to prepare the proteins, dock the ligands and visualize the complexes, respectively. Remdesivir, Lopinavir and Hydroxychloroquine were used as reference drugs. Pharmacokinetic properties of the ligands were obtained using AdmetSAR. The binding energies of the standard drugs ranged from -5.4 to -8.7 kcal/mol while over 400 of the ligands screened showed binding energy lower than -5.4 kcal/mol. Out of the 791 number of compounds docked, 10, 91, 132, 92, 54 and 96 compounds showed lower binding energies than all the controls against 3CLPro, ACE2, NSP3, NSP9, RP1a and RdRp, respectively. Ligands that bound all target proteins, and showed the lowest binding energies with good ADMET properties and particularly showed the lowest binding against ACE2 are ethynodiol diacetate (-15.6 kcal/mol), methylnaltrexone (-15.5 kcal/mol), ketazolam (-14.5 kcal/mol) and naloxone (-13.6 kcal/mol). Further investigations are recommended for ethynodiol diacetate, methylnaltrexone, ketazolam and naloxone through preclinical and clinical studies to ascertain their effectiveness.

Dataset Information

Inhibitory efficacy of 2, 4-diacetylphloroglucinol against SARS-COV-2 proteins: in silico study

Supplementary Information

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets