Current Approaches on Viral Infection: Proteomics and Functional Validations

Zheng, Jie; Tan, Boon Huan; Sugrue, Richard; Tang, Kai

Drug inhibitions specifically targeting viral proteins have been increasingly in demand to block virus infections. However, some viral proteins, e.g., hemagglutinin (HA) and neuraminidase of the influenza A virus, could exhibit their remarkable potentials to mutate to new subtypes. Thus it is necessary to require an updated drug discovery strategy to cope with prophylaxis upon virus infection. Clinically, there are two available drugs against neuraminidase: zanamivir and oseltamivir (Shahrour, 2001) . Oseltamivir, also known as tamiflu, was the first orally active neuraminidase inhibitor able to defend the H5N1 avian flu and H1N1 swine flu in early infection (Agrawal et al., 2010) . And zanamivir is effective to prevent symptomatic laboratoryconfirmed influenza virus and its transmission in healthy adults (Jackson et al., 2011) . In addition, adamantine is widely used to block the Matrix 2 (M2) ion channel in vaccine and antiviral drug designs. Nevertheless, both adamantine-resist and tamifluresist circulating influenza A virus strains were emerged in the last century (Deyde et al., 2007; Hayden and de Jong, 2011; Sheu et al., 2011) . Therefore, a strategy for updated drugs or vaccines targeting new viral mutants should be urgently established in preparation for the next pandemics or epidemics. The utility of proteomics has been efficiently employed to facilitate the vaccine design and antiviral drug discovery. For example, the binding between influenza HA and α-2, 6-sialylated glycoprotein receptor is the initial step to induce human infection. Also, the HA precursor is further cleaved by proteases on the virus surface to generate the C-terminal fragment HA1 and the N-terminal fragment HA2, triggering the potential ability of membrane fusion process (Wiley and Skehel, 1987) . Thus, HA or its binding with sialic acid receptors could be regarded as potential drug targets to block the initial stage of virus infection. To characterize the innate immunity antiviral components from salivary, Chen et al. purified the binding partners of α-2, 6-sialylated glycoprotein receptor. And Frontiers in Microbiology | Virology α-2-macroglobulin (A2M) was identified by proteomic approach for specifically inhibiting hemagglutination .