Antivirus agent, Ro 09-0410, binds to rhinovirus specifically and stabilizes the virus conformation

Inhibition of the uncoating of bovine enterovirus by short chain fatty acids

“…Our findings are similar to those described for a number of other compounds which are capable of inhibiting the uncoating of picornaviruses while not interfering with attachment and penetration of host cells (Lonberg-Holm & Noble-Harvey, 1973;Longberg-Holm et al, 1975;Ninomiya et al, 1984;Tisdale & Selway, 1984, Otto et al, 1985Smith et al, 1986;Kenny et al, 1988;Rossmann, 1989). Detailed studies by Rossmann and his colleagues, using X-ray crystallography, have shown that the antiviral activity of a series of compounds synthesized by the Sterling Winthrop Institute (WIN compounds) is due to a strong hydrophobic bonding occurring in a small pocket found in the floor of the canyon which encircles each of the 12 vertices on HRV-14 particles.…”

“…Mengovirus, which is structurally similar to HRV-14, has a partially blocked hydrophobic pocket which may influence accessibility to WIN compounds. The specificity of compounds such as the chalcone Ro 09-0410, which inhibits rhinoviruses but is ineffective against coxsackie-, echo-, polio-and mengoviruses (Ishutsuka et al, 1982;Ninomiya et al, 1984), the inhibition of HRV-2 but not HRV-14 by low concentrations ofSDS (Lonberg-Holm & Noble-Harvey, 1973) and the findings presented in this communication are less easy to explain and may argue against a common binding site. We cannot rule out the possibility that the poliovirus type 1 (a South African isolate made in 1986), HRV-1B and the coxsackievirus B5 used in this study (for which there are no structural data) may have inaccessible hydrophobic pockets.…”

“…An alternative explana-tion might be that there are other sites on some picornaviruses that interact with hydrophobic fatty acids in such a way that uncoating is inhibited. It has been proposed for the anti viral chalcone Ro 09-0410 that some rhinoviruses have specific binding sites on their capsids not found on other picornaviruses (Ninomiya et al, 1984). Competition studies with WIN compounds and RNA sequence analysis of escape mutants should go some way to answering this question.…”

Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus.

“…Sindbis virus has a lipid envelope with an internal nucleocapsid core somewhat similar to retroviruses. A variety of antiviral agents that inhibit viral uncoating have been reported for the rhino-and enterovirus members of the picornavirus family (14)(15)(16)(17). WIN 51711 is representative of a class of compounds that inhibit picornavirus replication in tissue culture (18) and in animal models of human enterovirus disease (19,20).…”

Comparative studies on the modes of action of the antirhinovirus agents Ro 09-0410, Ro 09-0179, RMI-15,731, 4',6-dichloroflavan, and enviroxime

“…1) directly inactivated only human rhinoviruses (HRV) (4). It bound to HRV at the specific site on the capsid protein not found on degraded HRV or viruses insensitive to the agent and stabilized the virus particles in such a way that HRV bound to the agent resisted the conformational change in virion size induced by low pH or elevated temperature (56°C) (11). We suggested that Ro 09-0410 interfered with the conformational change occurring during the uncoating process in the cells (11).…”