Three types of new molecules could interrupt P2X4 activation based on our findings: First, we can de novo design high affinity small molecules containing both the acidic group to interact with K70, 72, K316, K193, R298 and the heterocyclic group to finely match the shape of site 2 or 3. These small molecules can compete with ATP and meanwhile act as allosteric modulator to prevent the dynamics of head domain. The second type of molecules are designed to fill up the cleft between the head domain and the dorsal fin domain. This strategy has also been proposed by Jiang et al. as inhibitor binds to this position can prevent the closing of ATP-binding site jaw, an allosteric change essential for channel activation. PRRSV virulence is multigenic and resides in both the non-structural and structural viral proteins. The molecular characteristics, biological and immunological functions of the PRRSV structural and nonstructural proteins and their involvement in the virus pathogenesis were recently reviewed. The disease induced by PRRSV has many clinical manifestations but the two most prevalent are severe reproductive failure in sows and gilts and respiratory problems in pigs of all ages associated with a non-specific lymphomononuclear interstitial pneumonitis. App is the causative agent of porcine pleuropneumonia, a severe and highly contagious respiratory disease responsible for major economic losses in the swine industry worldwide. The disease, transmitted by aerosol or by direct contact with infected pigs, may result in rapid death or in severe pathology characterized by hemorrhagic, fibrinous, and necrotic lung lesions. Exposure to the organism may lead to chronic infection such that animals fail to thrive; alternatively, they survive as asymptomatic carriers that transmit the disease to healthy herds. Many virulence factors of this microorganism have been well characterized. To date, fifteen serotypes of App based on capsular antigens have been described. The prevalence of specific serotypes varies with geographic region. Recent advances in pathogen detection methods allow better understanding of interactions between pathogens, improve characterization of their mechanisms in disease potentiation and demonstrate the importance of polymicrobial disease. In the present study, the in vitro interactions between PRRSV and App in PRRSV permissive cell models were investigated. Thus, MARC145 cells, SJPL cell line and pulmonary alveolar macrophages were used in this study since they have been shown previously to be permissive to PRRSV infection and replication. Results indicate that App possesses a strong antiviral activity against PRRSV in vitro. Androgens are required for prostate development, growth and physiology, by activating the androgen receptor, which is expressed in both epithelial and stromal cells of the adult prostate gland. More than 300 proteins have been identified to contribute to AR activation and to modulate its transcription activity.