Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus that causes Coronavirus 2019 (COVID-19). To date, there has been no proven effective drug for the treatment or prevention of COVID-19. A study on developing inhibitors for this virus is carried out using molecular docking simulation methods. 3CL-Pro, PL-Pro, Helicase, N, E, and M protein were used as protein targets. Autodock Vina, Autodock 4.2, and PSOVina were used in this study. This study aims to obtain a model of ligands interactions of active natural compounds against the receptor protein encoded by the SARS-CoV-2 genome and their free binding energy to propose active compounds from natural products that have potential as a drug for COVID-19. Corilagin (-14,42 kcal/mol), Scutellarein 7-rutinoside (-13,2 kcal/mol), Genistein 7-O-glucuronide (-10,52 kcal/mol), Biflavonoid-flavone base + 3O (-11,88 and -9,61 kcal/mol), and Enoxolone (-6,96 kcal/mol) has the best free energy value at each protein target indicating that the compound has the potential as a viral protein inhibitor for further investigation. This research is limited to computer simulations, where the results obtained are still a prediction.
Kaurene diterpenoids were found in some plants such as Adenostemma lavenia and Pteris semipinnata to have antioxidant, antiinflammatory, anticancer, antitumor, cytotoxic, and antiviral activities. To evaluate the potency of kaurene diterpenoids as antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted an in silico study of several kaurene diterpenoids and antiviral drugs such as remdesivir and favipiravir in inhibition essential SARS-CoV-2 proteins including 3CLpro, Plpro, nucleocapsid (N), and membrane (M) through molecular docking, molecular dynamic (MD) simulations, adsorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetic properties prediction using a number of pieces of software. The docking study showed that the kaurene diterpene glycosides have a higher binding affinity to the 3CLpro, N, and M proteins of SARS-CoV-2 than other kaurene diterpenoids and even antiviral drugs such as remdesivir and favipiravir. Inhibition of these nonstructural and structural proteins has a significant impact on disrupting the viral replication and viral assembly of SARS-CoV-2. Almost all the complexes showed minimum deviation and fluctuation, indicating that each ligand is strongly bound to the binding site of proteins. ADMET prediction revealed all kaurene diterpenoids were well absorbed by the human intestine, noncarcinogenic, and did not cause mutations in DNA. Therefore, we expected these materials could be a potential preventive and therapeutic agent in the fight against the COVID-19 disease.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus that causes Coronavirus 2019 (COVID-19). To date, there has been no proven effective drug for the treatment or prevention of COVID-19. A study on developing inhibitors for this virus was performed using molecular dynamics simulation. 3CL-Pro, PL-Pro, Helicase, N, E, and M protein were used as protein targets. This study aimed to determine the stability of the selected protein-ligand complex through molecular dynamics simulation by Amber20 to propose bioactive compounds from natural products that have potential as a drug for COVID-19. Based on our previous study, the best value of free binding energy and protein-ligand interactions of the candidate compounds are obtained for each target protein through molecular docking. Corilagin (-14.42 kcal/mol), Scutellarein 7-rutinoside (-13.2 kcal/mol), Genistein 7-O-glucuronide (-10.52 kcal/mol), Biflavonoid-flavone base + 3O (-11.88 and -9.61 kcal/mol), and Enoxolone (-6.96 kcal/mol) has the best free energy value at each protein target. In molecular dynamics simulation, the 3CL-Pro-Corilagin complex was the most stable compared to other complexes, so that it was the most recommended compound. Further research is needed to test the selected ligand activity, which has the lowest free energy value of the six target proteins.
Abstract:Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the produced insulin. Morinda citrifolia has been widely used as herbal medicine to prevent and to treat diabetes as well as health supplements. It contains flavonoids which may act as an antidiabetic agent. One of the receptors that play a role in the treatment of diabetes is peroxisome proliferator-activated receptor -gamma (PPARγ) which responsible for insulin sensitization in adipose tissue. In this study, the interaction beetween flavonoids contained in noni fruit as ligands, and PPARγ was investigated by using the Autodock Vina software. Some flavonoids such as quercetin, kaempferol, nicotifloroside, narcissoside, and rutin were included in this study. Rosiglitazone, a known ligand for PPARγ was used as the standard. The result revealed that all the selected flavonoids showed binding energy ranging between -8,1 kcal/mol to -8,5 kcal/mol. Eventhough, when compared with rosiglitazone (-8.9 kcal/mol), the value of the binding energy of flavonoids was higher, but close to rosiglitazone. This suggests that those flavonoid compounds may show comparable potential with rosiglitazone as antidiabetic agent.
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