Antiviral Research 66 (2005) 9–12
Cranberry juice constituents affect influenza
virus adhesion and infectivity
E.I. Weiss
a, ∗
, Y. Houri-Haddad
a
, E. Greenbaum
b
, N. Hochman
a
,
I. Ofek
c
, Z. Zakay-Rones
b
a
Department of Prosthodontics, Faculty of Dental Medicine, Hebrew University-Hadassah, Jerusalem, Israel
b
Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
c
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel
Received 26 July 2004; accepted 2 December 2004
Abstract
Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation
of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM’s potential for inhibiting influenza virus adhesion to cells,
and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes
(H
1
N
1
and H
3
N
2
) and the B type was inhibited by NDM at concentrations of 125 g/ml or lower, which is at least 20-fold lower than
that usually found in cranberry juice. A dose–response effect of NDM on HA was demonstrated. The infectivity of the A and B types was
significantly reduced by preincubation with NDM (250 g/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney
(MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were
allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID
50
were observed. The effect
was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory
effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.
© 2005 Elsevier B.V. All rights reserved.
Keywords: Influenza; Cranberry; NDM; Antiviral effect
Influenza, a highly communicable acute respiratory dis-
ease, predisposes to a number of complications, resulting in
a severe worldwide economic burden. Prevention and con-
trol of both the annual influenza epidemics and its infrequent
but severe pandemic outbreaks are achieved by the use of
vaccines and newly emerging antiviral drugs.
These vaccines provide sometimes lower than desirable
protection, particularly in the immunocompromised and the
elderly, the two most susceptible subpopulations (Keren et
al., 1988; Admon et al., 1997). Furthermore, the vaccines
currently available are designated for intramuscular injec-
tion, resulting mainly in serum antibodies. It follows that a
negligible amount of mucosal antibodies are present at the
access site of the virus. In addition, vaccines are generally
∗
Corresponding author. Tel.: +972 2 6776142; fax: +972 2 6429683.
E-mail address: ervinw@md.huji.ac.il (E.I. Weiss).
unavailable in the early stages of a pandemic (WHO, 1999)
and antiviral drugs may be the only means of intervention.
Two classes of antiviral drugs are used:
(i) Anti-M2 inhibitors amantadine and rimantadine, effec-
tive against A strains only (WHO, 1980). A reduction
in the severity and duration of the signs and symptoms
is recorded when they are administered within 48 h of
disease onset (ACIP, 1996).
(ii) Neuraminadase inhibitors, effective against both A and
B viruses and better tolerated than the former. To date,
strains resistant to the drugs are not clinically important,
probably because they are not as virulent as the parental
strains. As prophylactics, these inhibitors are 70–90%
effective and may shorten the duration of illness by 1.5
days when used within the first 48 h (Treanor and Falsey,
1999; Hayden et al., 1999). Therefore, there is a need
0166-3542/$ – see front matter © 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.antiviral.2004.12.011