The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification.
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.
Oevermann
Anna
A
Veterinary Medicine Faculty, Institute of Veterinary Physiology, University of Zürich, Winterthurerstrasse 260, CH-8057, Zürich, Switzerland.
Engels
Monika
M
Thomas
Ursula
U
Pellegrini
Antonio
A
D000418:Albumins / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002918:Chymotrypsin / Q000737:chemistry; D003588:Cytopathogenic Effect, Viral; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D007768:Lactalbumin / Q000737:chemistry / Q000494:pharmacology; D009113:Muramidase / Q000737:chemistry / Q000494:pharmacology; D009499:Neutral Red; D010434:Pepsin A / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010796:Phthalic Anhydrides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D014357:Trypsin / Q000737:chemistry; D014709:Vero Cells
D000418:Albumins; D000998:Antiviral Agents; D007202:Indicators and Reagents; D010446:Peptide Fragments; D010796:Phthalic Anhydrides; D011506:Proteins; D009499:Neutral Red; C478070:3-hydroxyphthalic anhydride; D007768:Lactalbumin; D009113:Muramidase; D002918:Chymotrypsin; D014357:Trypsin; D010434:Pepsin A