@article{IsaacsMikasiObasaetal.2020,
  author    = {Isaacs, Darren and Mikasi, Sello Given and Obasa, Adetayo Emmanuel and Ikomey, George Mondinde and Shityakov, Sergey and Cloete, Ruben and Jacobs, Graeme Brendon},
  title     = {Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors},
  series = {Viruses},
  volume    = {12},
  journal   = {Viruses},
  number    = {9},
  issn      = {1999-4915},
  doi       = {10.3390/v12090936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211170},
  year      = {2020},
  abstract  = {The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-na{\"i}ve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.},
  language  = {en}
}
@article{SarukhanyanShityakovDandekar2020,
  author    = {Sarukhanyan, Edita and Shityakov, Sergey and Dandekar, Thomas},
  title     = {Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer},
  series = {Frontiers in Chemistry},
  volume    = {7},
  journal   = {Frontiers in Chemistry},
  number    = {920},
  issn      = {2296-2646},
  doi       = {10.3389/fchem.2019.00920},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199505},
  year      = {2020},
  abstract  = {The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.},
  language  = {en}
}