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ADS-J1 inhibits human immunodeficiency virus type 1 entry by interacting with the gp41 pocket region and blocking fusion-active gp41 core formation

, : ADS-J1 inhibits human immunodeficiency virus type 1 entry by interacting with the gp41 pocket region and blocking fusion-active gp41 core formation. Antimicrobial Agents and ChemoTherapy 53(12): 4987-4998

We previously identified a small-molecule anti-human immunodeficiency virus type 1 (anti-HIV-1) compound, ADS-J1, using a computer-aided molecular docking technique for primary screening and a sandwich enzyme-linked immunosorbent assay (ELISA) as a secondary screening method. In the present study, we demonstrated that ADS-J1 is an HIV-1 entry inhibitor, as determined by a time-of-addition assay and an HIV-1-mediated cell fusion assay. Further mechanism studies confirmed that ADS-J1 does not block gp120-CD4 binding and exhibits a marginal interaction with the HIV-1 coreceptor CXCR4. However, ADS-J1 inhibited the fusion-active gp41 core formation mimicked by peptides derived from the viral gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR), as determined by ELISA, native polyacrylamide gel electrophoresis, and circular dichroism analysis. Moreover, using a surface plasmon resonance assay, we found that ADS-J1 could bind directly to IQN17, a trimeric peptide containing the gp41 pocket region, resulting in the conformational change of IQN17 and the blockage of its interaction with a short D peptide, PIE7. The positively charged residue (K574) located in the gp41 pocket region is critical for the binding of ADS-J1 to NHR. These results suggest that ADS-J1 may bind to the viral gp41 NHR region through its hydrophobic and ionic interactions with the hydrophobic and positively charged resides located in the pocket region, subsequently blocking the association between the gp41 NHR and CHR regions to form the fusion-active gp41 core, thereby inhibiting HIV-1-mediated membrane fusion and virus entry.


PMID: 19786602

DOI: 10.1128/AAC.00670-09

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Paynter, Q., 2000: Factors affecting broom regeneration in Australia and their management implications. Broom regeneration following disturbance, with and without vertebrate herbivores, was studied at three contrasting sites with differing abundances of native plant species in the Shoalhaven River system in southern New South Wales. This study (init...

Eknoyan, G.; Siegel, M.B., 1971: Recovery from anuria due to malignant hypertension. JAMA 215(7): 1122-1125

Lucchi, M.; Duranti, L.; Melfi, F.; Mussi, A., 2010: Polymer self-locking clips for vascular control during minimally invasive pulmonary lobectomies. Journal of Thoracic and Cardiovascular Surgery 139(5): 1345-6, 1346.E1

Gravely, J.F., 1984: A study of the mandibular closure path in Angle Class III relationship. A cephalometric study has been made of patients with Angle Class III incisor relationships to discover the extent of any forward displacement of the mandible occurring during closure from the point of initial incisor contact to one in which the po...

Kawata M.; Kinugasa T.; Shirakabe T.; Shirakabe Y., 1988: The forehead lift in japanese. The forehead is an area where facial expressions such as grief, anger and surprise are clearly seen. It is also an area where the signs of aging appear; such as, horizontal wrinkles of the forehead, vertical wrinkles between the eyebrows and saggi...

Agadzhanyan A.M.; Navasardyan E.M., 1974: Comparative study of hybrids of some species of lycopersicon with lycopersicon hirsutum and lycopersicon hirsutum f glabratum. Biologicheskii Zhurnal Armenii 27(12): 54-59

Nagle R.B., 1980: Transmission electron microscope and scanning electron microscope observations on the prolonged sperm uterine relationship in hibernating bats. Anatomical Record: 156a

Hashimoto, M., 1979: Health care and medical systems in Japan. Comparative Medicine East and West 6(3): 163-183

Stewart James M., 1970: Organization of crystallographic computer systems. Pages 297-301:

Lavoie, M., 2005: Caring for a person in mourning. Perspective Infirmiere 2(3): 36-39