In Silico Studies on Development of Novel Virostatic Agents against Bluetongue Virus

The core of BTV is organized into three concentric structures of which VP7 protein forms the major core protein. The subcore consists of VP3 protein and the innermost part of the core is made of three minor proteins: VP1, VP4, and VP6. Earlier it was reported that core-like particles (CLPs) composed of viral VP7 and VP3 proteins were produced in order to study role of VP7 protein in intermolecular interactions in the BTV assembly process. Site specific mutational studies revealed that substitution of the single lysine residue of VP7 (Lys-255) by leucine abrogated CLP formation, indicating a critical role for this lysine. In the present study, homology modeling, mutagenesis, and docking studies were carried out in order to design potent leads in modulation of VP7 protein in abrogating CLP formation. 1. Introduction Bluetongue is an infectious noncontagious virus disease of ruminants caused by bluetongue virus of genus Orbivirus within the family Reoviridae. It is transmitted by biting midges of the Culicoides genus (Diptera: Ceratopogonidae). In addition to biting midges, BTV has been isolated from some arthropods, for example, sheep ked (Melophagus ovinus) [1] or some species of ticks [2, 3] and mosquitoes [4]. However, these are mechanical vectors with only a negligible role in disease epidemiology [5]. It can be directly transmitted from one animal to another through semen and transplacentally [6]. Bluetongue can also be spread by live attenuated vaccines against BTV or even by vaccines against other antigens contaminated with BTV [7, 8]. To date 26 distinct internationally recognized serotypes (based on the lack of cross-neutralization) of the virus have been identified. Cattle and goats are major hosts of the virus, but in these species infection is usually asymptomatic despite high virus levels, allowing the disease to circulate in the absence of any symptoms. Sheep and deer are usually the only species to exhibit symptoms of infection. The manifestations of bluetongue range from an unapparent to a fatal outcome depending on the serotype and strain of the virus, the species, breed, and age of the infected animal; older animals are generally more susceptible [9]. The worldwide economic losses due to bluetongue have not been expressed in exact numbers, but the estimate is 3 billion US$ a year [10]. The losses are both direct (death, abortions, weight loss, or reduced milk yield and meat efficiency) and, what is more important, indirect as a result of export restrictions for live animals, their semen, and some products such as fetal bovine serum.