No abstract

Monoclonal antibodies (Mabs) against the Urbani strain of the SARS-associated coronavirus (SARS-CoV) were developed and characterized for reactivity to SARS-CoV and SARS-CoV S, N, M, and E proteins using enzyme-linked immunoabsorbent (ELISA), radioimmunoprecipitation, immunofluorescence, Western Blot and microneutralization assays. Twenty-six mAbs were reactive to SARS-CoV by ELISA, and nine were chosen for detailed characterization. Five mAbs reacted against the S protein, two against the M protein, and one each against the N and E proteins. Two of five S protein mAbs neutralized SARS-CoV infection of Vero E6 cells and reacted to an epitope within amino acids 490-510 in the S protein. While two of the three non-neutralizing antibodies recognized at second epitope within amino acids 270-350. The mAbs characterized should prove useful for developing SARS-CoV diagnostic assays and for studying the biology of infection and pathogenesis of disease.

V-073, an enterovirus capsid inhibitor, was evaluated for its spectrum of antipoliovirus activity. V-073 inhibited all 45 polioviruses tested in a virus-induced cytopathic effect protection assay, with 50% effective concentration (EC 50 ) values ranging from 0.003 to 0.126 M. Ninety percent of the polioviruses tested were inhibited at EC 50 s of <0.076 M (MIC 90 ‫؍‬ 32 ng/ml). V-073 is a promising antiviral candidate for the posteradication management of poliovirus incidents.Polio eradication. The World Health Organization (WHO), Rotary International, the U.S. Centers for Disease Control and Prevention (CDC), and the United Nations International Children's Emergency Fund launched the Global Polio Eradication Initiative in 1988. The initiative is approaching its goal and expects the world to be certified polio free in the near future. Protecting the 25-year and more than $7 billion investment in polio eradication will depend on the policies, tools, and tactics available during the final stages of eradication and in the posteradication era. The global public health community must be equipped to protect against virus reintroduction and, in the event of reintroduction, to rapidly contain, control, and eliminate the virus.In November 2005, the National Research Council of the (U.S.) National Academies considered the potential role for antipoliovirus drugs in the eradication and posteradication management of poliovirus incidents. Currently, there are no antiviral drugs approved for treatment of poliovirus. The National Research Council concluded that there is indeed an important role for antivirals and recommended their immediate development (3). The case for developing antiviral drugs against poliovirus has been reviewed recently (2).Compound V-073. V-073 (Fig. 1), previously designated SCH 48973 (1), is a member of the picornavirus antiviral mechanistic class called capsid inhibitors. Antiviral compounds in this class inhibit picornaviruses by a virus-specific mode of action. These compounds integrate into the viral capsid at a specific site. Upon doing so, they prevent virus "uncoating" and the release of the viral RNA from the capsid, thereby blocking the initiation of the viral infection cycle (4). Other notable members of this class are pleconaril, disoxaril, and pirodavir. Unfortunately, these latter compounds lack the necessary antiviral potency and spectrum across poliovirus serotypes (2).V-073 was previously reported to have broad-spectrum antienterovirus activity, including activity against poliovirus type 2, both in cell culture and in a poliovirus challenge model with mice (1). However, since the compound was then being developed for nonpolio enterovirus indications, its spectrum of antipoliovirus activity was not explored. Here, we present virus susceptibility data that indicate V-073 has specific, potent, and broad-spectrum antipoliovirus activity. Together with its other pharmacological attributes (to be reported elsewhere), V-073 represents a promising poliovirus antiviral drug candidate. Antipoliovir...

93). The resistance phenotype was relatively stable upon passage of viruses in cell culture in the absence of drug. Single-step growth studies showed no substantial differences between drug-resistant variants and the virus stocks from which they were derived, while the resistant viruses were generally more thermally labile than the corresponding drug-susceptible parental viruses. These studies provide a foundation from which to build a greater understanding of resistance to antiviral compound V-073.