Molecular screening reveals Variolin B as a multitargeted inhibitor of lung cancer: a molecular docking-based fingerprinting and molecular dynamics simulation study

AbstractLung Cancer is the topmost death causing cancer and results from smoking, air pollution, cigar, exposure to asbestos or radon-like substances, and genetic factors. The cases of Lung Cancer in south Asian developing nations are being seen most due to heavy pollution and unbalanced lifestyle and putting a considerable burden on healthcare systems. The Food and Drug Administration of the USA has approved almost 100 drugs against SCLC and NSLC and a few drugs that are given to minimise the side effect of anticancer drugs. However, the drugs are shown to be resistant at significantly higher stages and non-affective on cancerous cells and have long-term side effects due to designing the drug by keeping one protein/gene target while designing or repurposing the drugs. In this study, we have taken five main lung cancer protein targets- Nerve growth factor protein (1SG1), Apoptosis inhibitor survivin (1XOX), Heat shock protein (3IUC), Protein tyrosine phosphate (3ZM3), Aldo-keto reductase (4XZL) and screened the complete prepared Drug Bank library of 155888 compounds and identified Variolin B (DB08694) as a multitargeted inhibitor against lung cancer using HTVS, SP and XP sampling algorithms followed by MM\GBSA calculation to sort the best pose. Variolin B is a natural marine antitumor and antiviral compound, so we analysed the ADMET properties and interaction patterns and then simulated all five P-L complexes for 100 ns in water using the NPT ensemble to check its selves against lung cancer. The docking results, ADMET and fingerprints have shown a good performance, and RMSD and RMSF results were with least deviation and fluctuations (<2Å) and produced a huge contact with other residues making the complex stable. The complexes initially fluctuated and deviated due to changes in the solute medium and sudden heat and stabilise after a few ns. However, extensive experimental validation is required before human use.Communicated by Ramaswamy H. SarmaKeywords: Lung cancermultitargeted drugsmolecular dockingVariolin Bdrug resistance Availability of data and materialAll the data are well reported in the manuscript that can be used to reproduce the results. No supplementary material is needed to be provided in addition.Consent for publicationAll authors consent to submit the manuscript to the Journal.Disclosure statementThe authors declare no competing or conflict of interest.Ethical responsibilitiesThis article is based on computational concepts, and the research does not physically involve any living organism or humans, so the ethical issues are not applicable.Additional informationFundingAuthors would like to acknowledge the support of the Deputy for Research and Innovation, Ministry of Education, Kingdom of Saudi Arabia, for this research through a grant (NU/IFC/02/MRC/-004) under the Institutional Funding Committee at Najran University, Kingdom of Saudi Arabia.