title: An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.
abstract: A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.
authors.affiliation: a Division of Toxicology , CSIR-Central Drug Research Institute , BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow 226031 , India.|b Academy of Scientific and Innovative Research (AcSIR) , New Delhi 110 001 , India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Omer
authors.affiliation: a Division of Toxicology , CSIR-Central Drug Research Institute , BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow 226031 , India.|b Academy of Scientific and Innovative Research (AcSIR) , New Delhi 110 001 , India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D027383:Papillomaviridae / Q000187:drug effects / Q000254:growth & development; D064798:Polypharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D039681:Pyranocoumarins / Q000737:chemistry / Q000494:pharmacology*; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000821:virology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D049490:Systems Biology / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D039681:Pyranocoumarins; D011714:Pyrans; D054852:Small Molecule Libraries; C032678:chaetochromin; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); C075959:calanolide A
keywords: AIDS-associated cancers; cancer; molecular docking; molecular dynamics; polypharmacology