Protein infectivity mechanism

Exploded view of the human immunodeficiency virus. It is an RNA (retrovirus) virus that contains surface proteins composed of a knoblike glycoprotein (gpl20) linked to a transmembrane stalk (gp41). These surface proteins are the infective mechanisms that allow the virus to bind to CD4 proteins of cells, such as T4 lymphocytes and monocytes. 

Protease inhibitors are targeted towards the HIV proteases, which are essential to activate precursors of gag-pol. HIV protease is essential for infectivity and cleaves the viral polyprotein (gag-pol) into active viral enzymes and structural proteins. The mechanism of action of these drags is by binding reversibly to the active site of HIV protease and blocking subsequent viral maturation. This major class includes saquinavir, ritonavir, indinavir, and nelfi-navir. Toxicities of protease inhibitors include nausea, vomiting, and diarrhea. 

Lingelbach, K., and Przyborski, J. M. (2006). The long and winding road protein trafficking mechanisms in the Plasmodium falciparum infected erythrocyte. Mol. Biochem. Parasitol. 147,1-8. 

In addition to their dietary importance, the proteins are the most abundant macromolecules in the cell, and they carry out most of the work in a cell. Protection of the body from infection, mechanical support and strength, and catalysis of metabolic reactions— all are functions of proteins that are essential to life. 

The mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

Thiosemicarba2ones have long been used as antiviral agents, principally against pox vimses of the vaccinia family. One compound of this series, the isatin derivative (6) C HgN OS, has been used prophylacticaHy to prevent outbreaks of smallpox in humans (10) and to inhibit the protein synthesis in poxvims-infected cells. The molecular mechanics relating to this property are still not known (11), though the binding of a metal ion may be a key factor... 

Petersen J, Dandri M, Mier W, Lfltgehetmann M, Volz T, von Weizsacker F, Haberkom U, Fischer L, Pollok JM, Erbes B, Seitz S, Urban S (2008) Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein, Nat Biotechnol 26 335-341 PorniUos O, Garrus JE, Sundquist WI (2002) Mechanisms of enveloped RNA virus budding. Trends CeU Biol 12 569-579... 

Apart from offering a new and highly specific approach to the inhibition of herpesviruses, this new mechanism of action could potentially also have beneficial immunological consequences. During treatment with BAY 38-4766, viral protein synthesis continues, but due to the lack of monomeric genomic length DNA, only empty particles (dense bodies) can be formed. It is conceivable that these non-infections viral particles could aid the establishment of an antiviral immune response, leading to better control of the virus by the host. This mechanism appears... 

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