New Approaches to the Prevention and Treatment of Viral Diseases

Abstract

The review discusses a new approach to the prevention and treatment of viral infections based on the use of pine needles polyprenyl phosphate (PPP) and associated with the infringement of prenylation process-the attachment of farnesol or geranyl geraniol to the viral protein. Currently, prenylation has been detected in type 1 adenovirus, hepatitis C virus, several herpes viruses, influenza virus, HIV. However, this list is far from complete, given that prenylated proteins play an extremely important role in the activity of the virus. We assume that the interferon produced in response to PPP may suppress expression of the SREBP2 transcription factor. As a result, the mevalonic acid pathway is violated and, as a result, the formation of early polyprenols precursors (geraniol, geranyl geraniol, farnesol), which are necessary for the prenylation of viral proteins, is blocked and the formation of mature, virulent virus particles is broken. As a consequence, the maturation of viral particles is inhibited, and defective particles are formed. Polyprenol was extracted from greenery (pine, fir and spruce needles, mulberry leaves, etc.), purified by chromatography, phosphorylated and identified by HPLC and NMR. Obtained PPP was used as antiviral in some experimental models in vitro and in vivo. During numerous studies, it was found that PPP manifested versatile antiviral effects, both in vitro and in vivo. The maximum effect was observed with viruses in which the presence of prenylated proteins was established, namely influenza A virus, HIV-1, tick-borne encephalitis virus, hepatitis A and C viruses, herpes simplex viruses type 1 and 2, some coronavirus. The available data obtained both in the experimental conditions and during clinical trials allow us to regard PPPs as safe and effective medicine for prevention and treatment of viral diseases.

Keywords: Coronavirus; Interferons; Plant polyprenols; Prenylation; SREBP2; Viral infection.

Fig. 1

Mevalonate pathway and stages of isoprenoid synthesis. OPP oxygen-pyrophosphate, HMG-CoA 3-hydroxy-3-methylglutaryl-CoA

Fig. 2

Posttranslational prenylation of proteins

Fig. 3

Formation of defective viral particles after exposure to PPP. Tick-borne encephalitis virions, 2 h after the addition of a placebo (bottom photo) or PPP (top photo)

Fig. 4

Content of SREBP2 in the liver lysate of mice after PPP administration

Fig. 5

Effect of PPP on lipoxygenase-5 activity

Fig. 6

PPP anti-herpetic activity. a treatment of herpetic meningoencephalitis (HSV type 1) in mice; b treatment of Aujeszky’s disease in rabbits; c treatment of experimental genital herpes infection (HSV type 2) in guinea pigs. The following signs of the disease were recorded: edema and hyperemia of the urethra and external genital organs; vesicular rash, exanthema, papules, pustules; erosive and erosive-ulcerative lesions, herpetic crusts; vaginal discharge; violation of the resorption of the vaginal contents of the vaginal mucosa. These symptoms were scored in the form of both individual symptoms and the symptom complexes, where 1 symptom is equal to 1 point. The effectiveness of the treatment was evaluated by changing the specific manifestations of the clinical signs of the disease localized on the female genitalia. TDSI means the total disease severity index, TEI means the therapeutic effect index, ADD means the average duration of the disease. d Inhibition of the symplast formation in Vero cells infected with HSV type 1. Mean inhibition percent 87 ± 1.81 (M ± m), p < 0.001

Fig. 7

Follicles of the ovary of a guinea pig infected with herpes simplex virus type 2 (a) and after treatment with PPP (b). Hematoxylin–eosin staining