3.5 Viral protein assembly
Capsid proteins have a pivotal function in the assembly of the virus, and interfering with the structure or function of these key proteins can be a solid antiviral strategy. Coronaviruses are distinct from other enveloped viruses in that they assemble at the intracellular membranes in the endoplasmic reticulum and golgi intermediate compartment (ERGIC) and transported out of the cell by exocytosis (Schoeman and Fielding, 2019). Envelope proteins (E) are clearly important for coronaviruses assembly, but their exact mechanistic role(s) is still not yet fully described (Schoeman and Fielding, 2019). Although E protein is abundantly expressed inside the infected cell, only a small portion is incorporated into the virion envelope and the major part is localized in intracellular trafficking, and participates in coronavirus assembly. The envelope protein (E) of coronaviruses (HCoV-229E, MHV, IBV) mediates viral assembly and form cation-selective ion channels that their function is not clear (Wilson et al., 2004). Involvement of E protein in critical aspects of the viral life cycle, make 2019-nCoVs lacking E protein, a promising vaccine candidate. Pharmacological blockage of its assembly with acylguanidine, cinnamoylguanidine reduced the SARS-CoV and MHV viral titer by 76 and 88% at a concentration of 10 µM, respectively (Gage et al., 2007).
Qin et al. designed siRNAs that inhibit M protein expression through degradation of M mRNA in SARS-associated coronavirus, which provides an approach for studies on the functions of M protein and for the development of novel therapeutic agents for CoV infection (Qin et al., 2007)
Application of viral assemble inhibitors for different types of viruses including Mo-MLV (McNally et al., 2010), CSFV (Zhou et al., 2008), HIV-2 (Wu et al., 1995), HIV-1 (Li et al., 2009), DENV2 (Qin et al., 2005), HBV (Seo et al., 2019) and influenza A (Liu et al., 2014) is investigated. However, no drug candidate disparting the 2019-nCoV assembly is in the trial or is reported so far.