Epidermal growth factor receptor mutant T790M-L858R-V948R inhibitor from Calophyllum inophyllum L. leaf as potential non-small cell lung cancer drugs

Context: Non-Small Cell Lung Cancer (NSCLC) is the most common lung cancer type, with 80-85% prevalence. Usually, NSCLC is treated by chemotherapy and radiotherapy in collaboration with gefitinib or other anticancer drugs. Those treatments have many adverse effects, such as shortness of breath, bleeding, fever, hair loss, and radiation pneumonitis. Lack of treatment options and numerous mutations greatly contribute to lung cancer's shocking death toll. Therefore, potential EGFR mutant inhibitors need to be analyzed. Aims: To identify potential inhibitors of an epidermal growth factor receptor (EGFR) mutant derived from Calophyllum inophyllum L. leaf using an in silico approach. Methods: In silico analysis and literature study were carried out. Secondary metabolite compounds from C. inophyllum were obtained through the PubChem database, and their biological activity and ADMET were analyzed. Molecular docking with EGFR wild-type (5FED) and mutant (5HG7) was carried out using PyRx. Furthermore, amino acid residues were analyzed using Discovery Studio. Results: Based on overall screening and molecular docking, a non-toxic compound with a low binding affinity with EGFR mutant protein is 4-[2-(4-nitrophenyl)ethylcarbamoyl]benzenesulfonyl. Moreover, interactions and hydrogen bonds at Ala743, Gly796, Leu718, Phe856, Leu844, and Val726 are known to play a crucial role in ATP binding inhibition toward the tyrosine kinase domain, resulting in EGFR mutant inhibition. Conclusions: 4-[2-(4-nitrophenyl)ethylcarbamoyl]benzenesulfonyl is one of the potential candidates as an EGFR mutant protein by ATP binding inhibition. However, in vitro and in vivo research needs to be performed to confirm these results. Keywords: anticancer drug; lung cancer; NSCLC; secondary metabolites; virtual screening

Identification of Potential Ebola Virus Nucleoprotein (EBOV NP) Inhibitor Derivate from Various Traditional Medicinal Plants in Indonesia: in silico study

Ebola virus disease is caused by Ebolavirus infection. Within infection, Ebola nucleoprotein (EBOV NP) is essential part for virus proliferation. Recent report showed that the outbreak was happened in Congo on February 2021. Although million cases were reported, the drug is remain unavailable. However, Indonesia had a high diversity of plants as traditional drugs. This research aimed to identify the traditional drug plants as potential inhibitor for EBOV NP. The SMILE notation of 65 identified compounds were collected from PubChem and 3D structured of EBOV NP (PDB ID: 4Z9P) was obtained from PDB. Molecular docking was conducted between selected compounds and EBOV NP. Clabistrin C was selected as a control. Complex of compounds EBOV NP and its amino acid residues were depicted by using Chimera X and LigPlot. Several potential compounds were selected for pharmacological activity prediction by PASS Online, toxicity analysis by ProTox-II, and drug likeness analysis with SWISSADME. Result showed that among the docked compound, hesperidin, cucurbitacin, ginsenoside RH2, and ginsenoside RO had lower binding energy compared to control. Moreover, all of those compounds had comparable hydrogen and hydrophobic interactions with EBOV NP. Further analysis showed it has potential biological function for Ebola disease, such as antiviral, antioxidant, and immunostimulant. All those compounds had low toxicity. As conclusion, there are four promising compounds that potentially inhibited the Ebolavirus proliferation

Identification Of Potential Activity Of Volatile Compounds Derived From Pogostemon Cablin Benth As Antiviral Of Sars-Cov-2

Objective: Coronavirus disease-19 (COVID-19) is global pandemic which caused by SARS-CoV-2 infection. Mechanism of infection is initiated by attachment between viral glycoprotein with ACE2 receptor in human cells. Furthermore, Indonesia had a massive diversity of plants with a high potency of drugs, such as Pogostemon cablin Benth. In brief, it contained of various volatile compounds with many therapeutic properties. Therefore, this research aimed to identify the ability of volatile compounds from Pogostemon cablin Benth as a potential inhibitor of SARS-CoV-2 spike glycoprotein. Methods: SMILE notation of 22 volatile compounds of Pogostemon cablin Benth were collected from PubChem and the 3D structure of SARS-CoV-2 glycoprotein (PDB ID: 6VXX) was obtained from PDB database. Simulation of interaction between volatile compound and glycoprotein was conducted by using Pyrx molecular docking. Moreover, the complex of compounds-glycoprotein was depicted by using Chimera and the amino acid residue was analysed by using LigPlot. Selected potential compounds were identified for biological activity prediction, drug-likeness, and toxicity analysis. Results: Analysis showed that among those volatile compounds, only caryophyllene oxide (-6.3 kcal/mol) naturally bind specific into RBD site as compared to the control. Furthermore, it had comparable hydrogen and hydrophobic interactions with glycoprotein. Further analysis showed it has strong potential biological function for antiviral with low toxicity. Conclusion: Caryophyllene oxide is considered as promising candidate compounds that inhibited viral infection through SARS-CoV-2 glycoprotein

Molecular docking of active compounds from traditional medicinal plants as ACE-2 protein (1R4L) inhibitor in searching for COVID-19 drug

Coronavirus disease known as COVID-19 is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 binds to the receptor binding-domain of ACE-2. By blocking it with a specific ligand, we can prevent SARS-CoV-2 binding and therefore prevent its cellular entry and injury. The number of COVID-19 cases is still increasing and yet only 2.5% of Indonesians are fully vaccinated. Moreover, up to now, a specific cure for COVID-19 has not been found yet. However, many traditional medicinal plants have the potency of becoming COVID-19 drugs. Therefore, this study aimed to examine various active compounds derivate from the traditional medicinal plant as an inhibitor of SARS-CoV-2 receptor in human cell termed as ACE2. The activity and drug-likeness of the active compounds were predicted and molecular docking were conducted to identify the interactions between ligands and ACE-2. Toxicity assay was also identified to predict the toxicity class, lethal dose, and organ toxicity. This study showed that indirubin has lower binding energy as compared to the sulabiroins A and MLN-4760 as comparative control and potent inhibitor control, respectively. Indirubin shared similar interaction with amino acid residue to ACE-2 as compared to control. Based on the research result, it was suggested that Indirubin could be developed as a promising compound for COVID-19 antiviral drugs. KEYWORDS: ACE-2 inhibitor, Antiviral drug, Coronavirus, Indirubin, Sulabiroins A

IDENTIFICATION POTENTIAL ACTIVITY OF VOLATILE COMPOUNDS DERIVED FROM POGOSTEMON CABLIN BENTH AS ANTIVIRAL OF SARS-COV-2

Objective: Coronavirus disease-19 (COVID-19) is global pandemic which caused by SARS-CoV-2 infection. Mechanism of infection is initiated by attachment between viral glycoprotein with ACE2 receptor in human cells. Furthermore, Indonesia had a massive diversity of plants with high potency of drugs, such as Pogostemon cablin Benth. In brief, it contained of various volatile compound with many therapeutic properties. Therefore, this research aimed to identify the ability of volatile compounds from Pogostemon cablin Benth as potential inhibitor of SARS-CoV-2 spike glycoprotein. Methods: SMILE notation of 22 volatile compounds of Pogostemon cablin Benth were collected from PubChem and the 3D structure of SARS-CoV-2 glycoprotein (PDB ID: 6VXX) was obtained from PDB database. Simulation of interaction between volatile compound and glycoprotein was conducted by using Pyrx molecular docking. Moreover, complex of compounds-glycoprotein was depicted by using Chimera and amino acid residue was analysed by using LigPlot. Selected potential compounds were identified for biological activity prediction, druglikeness, and toxicity analysis. Results: Analysis showed that among those volatile compounds, only caryophyllene oxide (-6.3 kcal/mol) that naturally bind specific into RBD site as compared to control. Furthermore, it had comparable hydrogen and hydrophobic interactions with glycoprotein. Further analysis showed it has strong potential biological function for antiviral with low toxicity. Conclusion: caryophyllene oxide is considered as promising candidate compounds that inhibited viral infection through SARS-CoV-2 glycoprotein

In-silico screening of inhibitor on protein epidermal growth factor receptor (EGFR)

The screening process to detect early-stage lung cancer is injurious to a patient's survival. Fortunately, there are natural compounds that have been acknowledged to possess anticancer properties, work as the protein binding inhibitors of lung cancer promotors: EGF and EGFR. The study aims to identify inhibitors of EGFR protein binding. Assessments were accomplished based on several parameters related to EGFR proteins, such as pathways, protein activity, conformational changes, and numerous information using the STRING database and KEGG pathway database. Ten inhibitor compounds that expressed highest activity were selected for further analysis were: (20R,22R)-5beta,6beta-Epoxy-4beta,12beta,20-trihy-droxy-1-oxowith-2-en-24-enolide, irinotecan, flavopyridol, teniposide, exatecan, daphnoretin, indirubin, topitecan, wentilactone, and evidiamine. The native ligand Lapatinib was used as positive control in this analysis. The analysis was accomplished by molecular docking using Vina 4 in the PyRx software. Interactions between the ligands and residues were investigated using LIGPLOT+ 2.2. The In-silico analysis of the ten candidate compounds revealed that (20R, 22R)-5beta, 6beta-Epoxy-4beta, 12beta, 20-trihydroxy-1-oxowith-2-en-24-enolide expressed the lowest binding energy value, which is -10.4 kcal/mol, indicated the closest binding energy value to Lapatinib as the control. Based on the interaction of amino acids, (20R,22R)-5beta, 6beta-Epoxy-4beta, 12beta, 20-trihydroxy-1-oxowith-2-en-24-enolide has excellent potential to be utilized as next inhibitor com- pound candidates for EGFR protein, because it binds to the Lys745 residue. It mirrors the positive control and has a binding energy on the range of the specified acceptable parameters