1HRV

HRV14/SDZ 35-682 COMPLEX

Summary for 1HRV

• Entry DOI: 10.2210/pdb1hrv/pdb
• Descriptor: HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP1), HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP2), HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP3), ... (5 entities in total)
• Functional Keywords: antiviral agents, icosahedral virus, virus
• Biological source: Human rhinovirus 14; More
• Cellular location: Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3B: Virion (Potential). Picornain 3C: Host cytoplasm (Potential). RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential): P03303 P03303 P03303 P03303
• Total number of polymer chains: 4
• Total formula weight: 94878.07

Authors

Oren, D.A.,Zhang, A.,Arnold, E. (deposition date: 1995-03-02, release date: 1995-06-03, Last modification date: 2024-05-22)

Primary citation

Rosenwirth, B.,Oren, D.A.,Arnold, E.,Kis, Z.L.,Eggers, H.J.
SDZ 35-682, a new picornavirus capsid-binding agent with potent antiviral activity.
Antiviral Res., 26:65-82, 1995

PubMed Abstract: SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml, without exerting any effect on cell proliferation up to 30 micrograms/ml. As observed with other capsid-binding antipicornavirus compounds, there is a wide variation in sensitivity of the different serotypes within the rhinovirus group. The point of interference of SDZ 35-682 in a single cycle of virus growth is an early event taking place before 2 or 3 h of echo- or rhinovirus replication, respectively. By incorporation of neutral red into the viral capsid and measurement of acquisition of photoresistance it is shown that uncoating of echovirus 9 is inhibited by SDZ 35-682. In addition, efficiency of adsorption of echovirus 9 is reduced by SDZ 35-682. To demonstrate that SDZ 35-682, like other uncoating inhibitors of picornaviruses, binds to the hydrophobic pocket beneath the canyon floor co-crystallization with HRV 14 was performed. Considerable conformational changes occur in VP1 in the HRV 14/SDZ 35-682 complex. SDZ 35-682 is 19 A long from end to end and thus fills the entire hydrophobic pocket including its innermost end; it is less flexible than other long antiviral agents. It has been suggested that compounds filling the entire hydrophobic pocket will affect the uncoating process of the virion. Thus, inhibition of viral uncoating, as demonstrated with echovirus 9, probably is the predominant mode of action of SDZ 35-682.

PubMed: 7741522
DOI: 10.1016/0166-3542(94)00066-H

Experimental method

X-RAY DIFFRACTION (3 Å)