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.