Computational exploration and molecular dynamics simulations for investigating the potential inhibitory mechanism of amantadine on the ion channel activity of bovine viral diarrhea virus p7

Tautz N, Tews BA, Meyers G (2015) The molecular biology of pestiviruses. Adv Virus Res 93:47–160. https://doi.org/10.1016/bs.aivir.2015.03.002

Article  CAS  PubMed  Google Scholar 

Chi S, Chen S, Jia W et al (2022) Non-structural proteins of bovine viral diarrhea virus. Virus Genes 58:491–500. https://doi.org/10.1007/s11262-022-01914-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gladue DP, Holinka LG, Largo E et al (2012) Classical swine fever virus p7 protein is a viroporin involved in virulence in swine. J Virol 86:6778–6791. https://doi.org/10.1128/JVI.00560-12

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harada T, Tautz N, Thiel H-J (2000) E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. J Virol 74:9498–9506. https://doi.org/10.1128/jvi.74.20.9498-9506.2000

Article  CAS  PubMed  PubMed Central  Google Scholar 

Largo E, Gladue DP, Torralba J et al (2018) Mutation-induced changes of transmembrane pore size revealed by combined ion-channel conductance and single vesicle permeabilization analyses. Biochim Biophys Acta Biomembr 1860:1015–1021. https://doi.org/10.1016/j.bbamem.2018.01.012

Article  CAS  PubMed  Google Scholar 

Largo E, Verdiá-Báguena C, Aguilella VM et al (2016) Ion channel activity of the CSFV p7 Viroporin in surrogates of the ER lipid bilayer. Biochim Biophys Acta 1858:30–37. https://doi.org/10.1016/j.bbamem.2015.10.007

Article  CAS  PubMed  Google Scholar 

Aldabe R, Barco A, Carrasco L (1996) Membrane permeabilization by poliovirus proteins 2B and 2BC. J Biol Chem 271:23134–23137. https://doi.org/10.1074/jbc.271.38.23134

Article  CAS  PubMed  Google Scholar 

Largo E, Gladue DP, Huarte N et al (2014) Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific Viroporin function. Antiviral Res 101:30–36. https://doi.org/10.1016/j.antiviral.2013.10.015

Article  CAS  PubMed  Google Scholar 

Pinto LH, Holsinger LJ, Lamb RA (1992) Influenza virus M2 protein has ion channel activity. Cell 69:517–528. https://doi.org/10.1016/0092-8674(92)90452-i

Article  CAS  PubMed  Google Scholar 

Clarke D, Griffin S, Beales L et al (2006) Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biol Chem 281:37057–37068. https://doi.org/10.1074/jbc.M602434200

Article  CAS  PubMed  Google Scholar 

Gonzalez ME, Carrasco L (2003) Viroporins. FEBS Lett 552:28–34. https://doi.org/10.1016/s0014-5793(03)00780-4

Article  CAS  PubMed  Google Scholar 

Pavlović D, Neville DCA, Argaud O et al (2003) The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain Iminosugar derivatives. Proc Natl Acad Sci USA 100:6104–6108. https://doi.org/10.1073/pnas.1031527100

Article  CAS  PubMed  PubMed Central  Google Scholar 

Griffin SDC, Harvey R, Clarke DS et al (2004) A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol 85:451–461. https://doi.org/10.1099/vir.0.19634-0

Article  CAS  PubMed  Google Scholar 

Jumper J, Evans R, Pritzel A et al (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589. https://doi.org/10.1038/s41586-021-03819-2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abraham MJ, Murtola T, Schulz R et al (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25. https://doi.org/10.1016/j.softx.2015.06.001

Article  Google Scholar 

OuYang B, Xie S, Berardi MJ et al (2013) Unusual architecture of the p7 channel from hepatitis C virus. Nature 498:521–525. https://doi.org/10.1038/nature12283

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eberhardt J, Santos-Martins D, Tillack AF, Forli S (2021) AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 61:3891–3898. https://doi.org/10.1021/acs.jcim.1c00203

Article  CAS  PubMed  PubMed Central  Google Scholar 

McNutt AT, Li Y, Meli R et al (2025) GNINA 1.3: the next increment in molecular docking with deep learning. J Cheminform 17:28. https://doi.org/10.1186/s13321-025-00973-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Vass M, Shi D et al (2023) Benchmarking refined and unrefined AlphaFold2 structures for hit discovery. J Chem Inf Model 63:1656–1667. https://doi.org/10.1021/acs.jcim.2c01219

Article  CAS  PubMed  Google Scholar 

Watson JL, Juergens D, Bennett NR et al (2023) De Novo design of protein structure and function with rfdiffusion. Nature. https://doi.org/10.1038/s41586-023-06415-8

Article  PubMed  PubMed Central  Google Scholar 

Suhag K, Borkotoky S, Siddiqui SI et al (2025) Mechanistic insights into the divergent membrane activities of a viroporin from chikungunya virus and its transframe variant. ACS Infect Dis. https://doi.org/10.1021/acsinfecdis.4c00562

Article  PubMed  Google Scholar 

Nieva JL, Madan V, Carrasco L (2012) Viroporins: structure and biological functions. Nat Rev Microbiol 10:563–574. https://doi.org/10.1038/nrmicro2820

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen X, Wang X (2024) Computational investigation in inhibitory effects of amantadine on classical swine fever virus p7 ion channel activity. Sci Rep 14:20387. https://doi.org/10.1038/s41598-024-71477-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Behmard E, Abdolmaleki P, Taghdir M (2018) Understanding the inhibitory mechanism of BIT225 drug against p7 viroporin using computational study. Biophys Chem 233:47–54. https://doi.org/10.1016/j.bpc.2017.11.002

Article  CAS  PubMed  Google Scholar 

Wei S, Hu X, Du L et al (2021) Inhibitor development against p7 channel in hepatitis C virus. Molecules 26:1350. https://doi.org/10.3390/molecules26051350

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown E, Swinscoe G, Lefteri DA et al (2024) Inhibitors of the small membrane (M) protein viroporin prevent Zika virus infection. Elife 13:e68404. https://doi.org/10.7554/eLife.68404

Article  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif