ANTIVIRAL EFFECTS OF SAIKOSAPONINS ON HUMAN CORONAVIRUS
(Department of Biotechnology, Tajen University, Pingtung, Taiwan)
Recently, a novel human coronavirus (HCoV) was identified as a causative agent of the severe acute respiratory syndrome (SARS).
1. Both HCoV-229E and HCoV-OC43 are HCoV that have been recognized for the past 30 years
2. Of the two, HCoV-229E has been recently recognized as an important cause of NRVI in high-risk infants.
3. Over the past decades, a number of phytochemicals have been reported to possess potent antiviral activity.
4. Saikosaponins represent a group of oleanane derivatives, usually as glucosides, that are found in a number of plant families.
Saikosaponins isolated from medicinal plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia scorodonia have been reported to possess various biological activities, namely antihepatitis, antinephritis, antihepatoma, anti-inflammation and antibacterial effects, as well as being able to modulate immune function.
Furthermore, saikosaponins (A, B2, C and D) have been shown to be active against human immunodeficiency virus (HIV), measles, influenza virus, herpes simplex virus and varicella-zoster virus.
In an attempt to find new anti-HCoV compounds, we conducted a series of experiments to investigate the antiviral activity and mode of action of saikosaponins against HCoV-229E in vitro.
Natural products from plants and micro-organisms have history- allies provided many valuable leads in the quest for new medicines to the pharmaceutical industry.
Over the past decades, many compounds isolated from medicinal plants have been shown to have inhibitory action against viruses.
In many countries, viral infection remains a serious issue, combined with the recent outbreak of SARS, for which no effective treatment is available, and scientists around the world are looking for new therapies for this disease.
The present study indicates that HCoV-229E has a potent activity against saikosaponin B2. With more research and a deeper understanding of the molecular way of behaving, saikosaponin B2 may be a novel lead for a new chemopreventive agent for this viral infection to be identified.
In previous studies, triterpenoid saponins have been shown to have marked antiviral activity in con-centrations where saponin displayed no cytotoxic impact on vero cells.
The antiviral activity mechanism was suggested to be correlated with an early event in the viral infectious cycle by inhibiting virus – host cell attachment based on a direct interaction of saikosaponin D with the host cell surface membrane.
In the present research, we postulated that the anti-HCoV-229E antiviral activity of saikosaponin B2 may be caused by direct inactivation of the virus or by direct interaction with the host cell membrane, resulting in morphological changes of the cell membrane. Consequently, such events may result in a viral adsorption and penetration arrest.
While saikosaponins have been shown to have an inhibitory effect against herpes simplex type I (HSV-1) in vitro in previous studies, the mechanism of action was not elucidated.
In another study, saikosaponin C showed involvement in the inhibition of hepatitis B virus DNA replication.
Saikosaponin B2 inhibited the attachment of HCoV-229E to the host cells and thus contributed to the arrest of viral absorption and even-tual viral penetration.
In addition to affecting viral attachment, saiko-saponin B2 also tends to prevent HCoV-229E from penetrating into host cells, as seen in the penetration experiment, in which HCoV-229E has failed to bind to host cells. The addition of saikosa- ponins was observed to block the penetration of HCoV-229E, indicating that saikosaponin B2 affects the cycle of viral penetration, probably by detaching viruses that have already bonded to the cell, likely by disrupting viral glycoproteins.
In addition, saikosaponin B2 has been found in this study to:
(i) inhibit HCoV-229E viral infection at concentrations of 25 mmol / L or less;
(ii) inhibit dose-dependent viral attachment to cells;
(iii) block viral penetration into cells; and
(iv) interfere with the early stage of viral replication, such as the absorption and penetration of viruses.
Saikosaponin B2’s various modes of action warrant further study.