Enveloped virus inhibitor

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Many enveloped viruses share a common mechanism of fusion, mediated by a virus-encoded glycoprotein that contains heptad repeats in its extraceUnlar domain. Dnring the fnsion process, these domains rearrange to form highly structured and thermodynamically stable coiled-coils. Viruses encoding fusion proteins that have these domains inclnde members of the paramyxovirus family (e.g., respiratory syncytial virus, metapneumovirus, and measles virus), ebola virus, influenza, and members of the retroviridae (e.g., human T cell lenkemia virus type-1 and human immunodeficiency virus type-1, HlV-1). Peptide inhibitors of fusion that disrupt the... 

Some compounds known to be inhibitors of peptidoglycan formation in bacteria have proved also to inhibit the lipid pathway of glyco-sylation of proteins. Moreover, these compounds show antiviral activity, because the maturation of enveloped virus in eukaryotic cells is impaired if glyeosylation of viral glycoproteins is inhibited (see Section IV). 

Abstract The inhibitory action of polyanionic substances on virus replication was reported more than 50 years ago. Seaweeds, marine invertebrates, and higher plants represent abundant sources of novel compounds of proved antiviral activity. Natural sulfated polysaccharides (SPs) are potent in vitro inhibitors of a wide variety of enveloped viruses, such as herpes simplex virus (HSV) types 1 and 2, human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), dengue virus (DENV), respiratory syncytial virus (RSV), and influenza A virus. Several polysulfate compounds have the potential to inhibit virus replication by blocking the virion binding to the host cell. In contrast, their in vivo efficacy in animal and human systemic infections has undesirable draw-... 

Hayashi, T., Hayashi, K., Maedaa, M., and Kojima, I. (1996b). Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulina platensis. ]. Nat. Prod. 59, 83-87. 

Heparin and other sulfated polysaccharides extracted from sea algae were found to be potent and selective inhibitors of the HIV-1 replication in cell culture as well as various enveloped viruses, including viruses that emerge as opportunistic pathogens (eg, herpes simplex virus and cytomegalovirus) in immuno-suppressed [eg, AIDS (the acquired immune deficiency syndrome)] patients. As potential anti-HIV drug candidates, sulfated polysaccharides offer a number of promising features (209,210). 

M. Baba, R. Snoeck, R. Pauwels, and E. de Clercq, Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus, Antimicrob. Agents Chemother., 32 (11), 1742-1745,1988. 

The inhibitory effects of polyaifionic substances on the replication of HSV and other viruses were reported almost five decades ago. Shortly after the identification of HIV as the causative agent of AIDS in 1984, heparin and other sulfated polysaccharides were found to be potent and selective inhibitors of HfV-1 replication in cell culture. Since 1988, the activity spectrum of the sulfated polysaccharides has been shown to extend to various enveloped viruses, including HSV in vitro (Karmakar et al. 2010 Herold et al. 1995), human cytomegalovirus (HCMV) (Baba et al. 1988), respiratory syncytial virus, influenza A and B virus (Damonte et al. 1994), DENV-2 and DENV-3 in the human hepatoma HepG2 (Talarico et al. 2005). 

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... 

Abstract The entry of viruses into target cells involves a complex series of sequential steps, with opportunities for inhibition at every stage. Entry inhibitors exert their biological properties by inhibiting protein-protein interactions either within the viral envelope (Env) glycoproteins or between viral Env and host-cell receptors. The nature of resistance to entry inhibitors also differs from compounds inhibiting enzymatic targets due to their different modes of action and the relative variability in... 

Ho HT, Fan L, Nowicka-Sans B, McAuhffe B, li CB, Yamanaka G, Zhou N, Fang H, Dicker 1, Dalterio R, Gong YF, Wang T, Yin Z, Ueda Y, MatiskeUa J, Kadow J, Qapham P, Robinson J, Colonno R, Lin PF (2006) Envelope conformational changes induced by human immunodeficiency virus type 1 attachment inhibitors prevent CD4 binding and downstream entry events. 

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