The lack of wide-spectrum effective antivirals and the emergence of drug-resistant strains dictate the urgent need to find out new preparations that can alleviate viral infections. In this regard, herbal medicines are of great scientific interest and have significant research potential. Medicinal plants' antiviral action has been confirmed by many studies, particularly against human immunodeficiency virus [1, 2], influenza , herpes simplex , and hepatitis . Plant biologically active compounds (BAC) summarized effect could be more effectively used to treat viral infections than single BAC. The advantage of herbal remedies compared with drugs of chemical origin may be considered the lower likelihood of causing resistant forms of virus occurrence .
Despite the availability of several effective vaccines, COVID-19 coronavirus infection and its treatment remain one of the world's top public health problems. At the same time, other viral infections continue to circulate in the population, although attention to them has somewhat declined due to pandemic COVID-19 . Therefore, the search for antiviral drugs is relevant primarily for uncontrolled viral infections, such as herpes, hepatitis, coronaviruses, and influenza. It should be conducted both on models of viruses and their surrogate models.
Our herbal preparation is an alcoholic extract of six plants used in official and traditional medicine - Filipendula vulgaris roots, Petroselinum crispum roots, Apium graveolens roots, Gallium verum herb, Linaria vulgaris herb, and Calendula officinalis flowers .
Biologically active substances of this phytopreparation resemble in their structures endogenous estrogens but without estrogen-like activity. Therefore, phytopreparation has a selective antiestrogenic activity, which normalizes the imbalance of gonadotropic hormones and the menstrual cycle’s second (luteal) phase. Phytopreparation has a pronounced effect on glandular tissue and stromal elements of the mammary glands, ovaries, and uterus, exhibits antiproliferative and anti-inflammatory properties, prevents the development of dysplastic processes in these tissues . It is used to treat menstrual disorders, fibrocystic mastopathy, retentional ovarian cysts. As part of complex therapy, phytopreparation is used to treat endometrial hyperplasia, uterine fibroids, endometriosis, and polycystic ovary syndrome .
The composition of the phytopreparation includes medicinal plants from different families, accumulating various groups of BAC, which have the potential for use not only in reproductive endocrinology.
The results of numerous scientific studies confirm that phenolic compounds contained in high concentrations in the raw material of this phytopreparation, especially phenolic acids (gallic, ellagic, salicylic acids), flavonoids (quercetin, rutin, apigenin kaempferol, catechin, epicatechin, and their derivatives) and other polyphenols are able to normalize a large number of enzymes and enzymatic systems, which are involved in the regulation of cell division and proliferation, platelet aggregation, detoxification, inflammation and the immune response development. These compounds have an antioxidant, anticancer, and immunomodulatory effect and cause a positive impact on hemostasis .
Scientific publications present a significant number of studies on the pronounced antiviral activity of these plant materials. Flavonoids (apigenin from Petroselinum crispum , apiin from Petroselinum crispum and Apium graveolens, pectolinarin, isolinariin, and pectolinarigenin from Linaria vulgaris [11–16]) are of particular interest among phytopreparation's phenolic active pharmaceutical ingredients. Flavonoids' antiviral activity has been actively studied for the last three decades. The first studies of apigenin and Acyclovir combined use demonstrated antiviral activities increase in experiments on cell culture with human alphaherpesviruses type 1 and 2 (HHV-1 and HHV-2) (formerly named herpes simplex viruses 1 and 2) . This encouraged further studies of the antiviral activity of herbal remedies containing apigenin and its derivatives.
Flavonoids (quercetin from Filipendula vulgaris [16, 17], kaempferol from Petroselinum crispum , spireoside and isoquercitrin from Filipendula vulgaris ) are also promising active substances with antiviral activity. Selway J.W.T.  found out that quercetin, morin, rutin, dihydroquercetin, dihydrophysetin, leukocyanidin, pelargonidin and catechin have antiviral activity against seven types of viruses, including herpes simplex viruses, respiratory syncytial virus, poliovirus, Syndbis virus, etc. It is believed that the mechanism of such action is realized via viral polymerase activity inhibition. Quercetin and quercetin-3-rutinoside inhibited the reproduction of HHV-1 and HHV-2, adenoviruses types 3, 8, 11 .
According to Bogdanova N.S. et al. , Calendula officinalis flowers tincture inhibits the replication of herpes simplex viruses, influenza A2, and influenza APR-8 viruses in vitro. Calendula's glycosylated flavonols rutin and isorhamnetin are supposed to suppress H1N1 influenza viruses . In vitro studies have shown that isorhamnetin inhibits the pseudotyped SARS-CoV-2 virus entering HEK293 (ACE2) cells [23, 24].
Hydroxycinnamic acids, which are present in significant quantities in Galium verum, Filipendula vulgaris, Calendula officinalis and Linaria vulgaris, have proven antiviral properties against infectious bronchitis virus (IBV) in vivo and in vitro . Xanthophyll lutein, which is contained in the raw material of Calendula officinalis, effectively inhibits the transcription of the hepatitis B virus . Petroselinum crispum and Apium graveolens could be a promising source of furanocoumarins with antiviral activity through psoralen, bergapten, xanthotoxin, and coumarin - umbelliferon. It was shown, for example, that psoralen had antiviral activity against HHV-1 and influenza virus . For substances of the furanocoumarin group, including bergapten and xanthotoxin, Ba Wool Lee et al. [28, 29] proved the presence of antiviral activity against influenza viruses H1N1 and H9N2 due to influenza virus, HHV-1, and Coxsackievirus B3 replication cycle's early phase inhibition.
Galium verum triterpene saponins, in particular, lupeol and ursolic acid, have antiviral potential in the case of rotavirus infections, as ursolic acid inhibits the early stages of the rotavirus replication cycle . The components of Petroselinum crispum and Apium graveolens essential oils (such as myristicin and apiol [31, 32]) have pronounced antifungal and antibacterial effects , which helps to alleviate concomitant disorders and to prevent the biofilms formation. Antiviral activity has been demonstrated for well-known flavonoids and other groups of biologically active substances . Therefore, our complex phytopreparation antiviral activity confirmation is of scientific interest and may have practical significance as a new safe antiviral agent.
The aims of this study were:
As phytopreparation's antiviral action is supposed to involve the interferon system, its interferon-inducing activity was also evaluated when studying the mechanism of antiviral action.