Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus

Björck, Lars; Grubb, Anders; Kjellén, Lars

doi:10.1128/jvi.64.2.941-943.1990

Cited by 158 publications

(61 citation statements)

References 17 publications

(9 reference statements)

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“…This might, on one hand, be due to the cell damage caused by viral multiplication that allows the compound to penetrate into the cell. Such a mechanism has been postulated for cystatin C, (Björk et al, 1990). On the other hand, the binding of the modified proteins to the viral envelope glycoproteins could be taken as a basis to explain an inhibition at the intercellular or extracellular level.…”

Section: Discussionmentioning

confidence: 96%

The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification

et al. 2003

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Chemical modification of the proteins bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin and chicken lysozyme by 3-hydroxyphthalic anhydride (3-HP) yielded compounds which exerted antiviral activity in vitro as compared with the native unmodified proteins. Of the three enveloped viruses tested, human herpes simplex virus type 1 (HSV-1), bovine parainfluenza virus type 3 and porcine respiratory corona virus, only HSV-1 proved sensitive to the 3-HP-proteins. All of the chemically modified proteins presented antiviral activity against HSV-1 when assayed before, during or after infection. However, to achieve HSV-1 inhibition, significantly higher concentrations of the modified proteins were required if present before infection as compared to during or after infection. Our results suggest that multiple mechanisms are involved in the inhibition of HSV-1 infection. Proteolytical digestion of albumin, alpha-lactalbumin, beta-lactoglobulin and lysozyme by trypsin, chymotrypsin and pepsin yielded several peptide fragments with antiherpetic activity. Chemical modification of these peptide fragments by 3-HP generated peptides with antiviral activity, however, this was almost always combined with a cytotoxic effect on the Vero cells. Overall, our results suggest that targeted chemical modification of some natural products might provide compounds effective against HSV-1 infection.

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Section: Discussionmentioning

confidence: 96%

The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification

et al. 2003

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“…Hence, inhibitors that would efficiently target the cysteine proteases of the parasite, while maintaining some selectivity distinguishing them from the homologous host enzyme, would be ideal drug leads. Cystatin C has also been shown to exhibit antiviral functions, as suggested from experiments done with polio, herpes simplex, and corona virus-infected cell lines (3,5). We previously elucidated the dual role of cystatin of suppressing the functional differentiation of Th2 type CD4 ϩ T cells, leading to the augmentation of the Th1 response, and up-regulating NO, resulting in the elimination Leishmania parasites in both in vitro and in vivo murine models of visceral leishmaniasis (6).…”

Section: Discussionmentioning

confidence: 98%

Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease

Mukherjee

Ukil

Das

2007

Antimicrob Agents Chemother

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Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its potential to induce nitric oxide (NO) generation from macrophages. Cysteine protease-inhibitory activity and NO-up-regulatory activity correspond to different regions, as revealed by the dissection of cystatin cDNA into nonoverlapping fragments. By using synthetic overlapping peptides, the NO-up-regulatory activity was found to be confined to a 10-mer sequence. In addition to having reasonable inhibitory effects on amastigote multiplication within macrophages (50% inhibitory concentration, 5.2 g/ml), 97 and 93% suppression, respectively, of liver and spleen parasite burdens was achieved with the 10-mer peptide at a dose of 0.5 mg/kg of body weight/day, given consecutively for 4 days along with a suboptimal dose of gamma interferon in a 45-day mouse model of visceral leishmaniasis. Peptide treatment modulated the levels of cytokine secretion by infected splenocytes, with increased levels of interleukin-12 and tumor necrosis factor alpha and increased inducible NO synthase production, and also resulted in resistance to reinfection. The generation of a natural peptide from cystatin with robust immunomodulatory potential may therefore provide a promising therapeutic agent for macrophage-associated diseases.

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“…Human cystatin C, obtained from human serum, and human stefin B, obtained from spleen, also bind and inhibit poliovirus protease 3C and block the replication of poliovirus in cultured cells (Korant et al, 1985(Korant et al, , 1986. Not only cystatin C, but also peptides that mimic the proteinase-binding center of cystatin C, such as Z-LVG-CHNHz (N-benzyloxycarbonylleucyl-valyl-glycine diazomethylketone), show antiviral activity against poliovirus and herpes simplex virus (see Section 4.2.2) (Bjorck et al, 1990).…”

Section: Cystatin Cmentioning

confidence: 99%

“…The use of peptides that mimic the viral cleavage site provides a potential for the development of new protease inhibitors, because they inhibit protease function (Green and Shaw, 1981). Therefore, analogues of the recognition site of viral proteases have a modified C-terminal or the N-terminal blocks viral replication (Bjorck et al, 1990;Korant, 1990). Tri-, tetra-or pentapeptides having, in the C-terminal, chloromethyl ketone or methyl ketone moieties, were active against poliovirus and rhinovirus (Kettner and Korant, 1987).…”

Section: Peptidyl Diazomethyl and Chloromethyl Ketonesmentioning

confidence: 99%

Picornavirus inhibitors

Carrasco

1994

Pharmacology & Therapeutics

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Picornaviruses are among the best understood animal viruses in molecular terms. A number of important human and animal pathogens are members of the Picornaviridae family. The genome organization, the different steps of picornavirus growth and numerous compounds that have been reported as inhibitors of picornavirus functions are reviewed. The picornavirus particles and several agents that interact with them have been solved at atomic resolution, leading to computer-assisted drug design. Picornavirus inhibitors are useful in aiding a better understanding of picornavirus biology. In addition, some of them are promising therapeutic agents. Clinical efficacy of agents that bind to picornavirus particles has already been demonstrated.

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Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus

Cited by 158 publications

References 17 publications

The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification

The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification

Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease

Picornavirus inhibitors

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