Therapeutic potential of natural plant substances for the control of avian infectious bronchitis virus
Abstract
Avian infectious bronchitis (IB) is one of the foremost avian pathologies and is caused by a coronavirus with worldwide distribution. In addition to its infectivity, the appearance of new variants and strains makes this pathology particularly difficult to control, which represents a threat to the poultry sector. Natural substances have long been used as therapeutic sources and boosters for vaccines since vaccines alone do not provide complete protection due to continuous mutations of the infectious bronchitis virus (IBV). To explore other remedies to fight IBV, several researchers have turned to using medicinal plants and extracting active ingredients with antiviral properties. The quest for alternative therapies is particularly relevant given the Sars-CoV-2 outbreak, a human coronavirus that shares similarities with IBV, such as its mutation rates and health complications. This article is a systematic review of natural products used against IBV. Thirteen natural products, including plants, essential oils, and mixtures, were identified in this study, and all showed antiviral activity against IBV, with variable effectiveness. Although the efficacy of these active substances has been established and demonstrated by scientific methods, further and more in-depth studies should be carried out to confirm the results, determine the mechanisms of action, and validate their use as a treatment or adjuvant.
Keywords: Coronavirus, IBV, plants, antiviral, poultry
INTRODUCTION
In the wake of the Sars-CoV-2 pandemic, developing effective anti-coronavirus drugs has become crucial for facing the global impact of the virus. Indeed, Covid-19 has proven to be hard to combat, creating a situation of urgency amongst researchers and scientists striving to find an effective antiviral treatment (Touil et al., 2023). While there has been real progress in antiviral drug development (Rhazzar et al., 2025), researchers used results from other coronavirus strains to gain insights and further their studies, such as Avian Infectious Bronchitis Virus (IBV) in poultry.
Virus infections are a concern in the poultry industry worldwide due to the considerable economic losses they entail. Some avian viruses are high priority and economically important, such as avian influenza virus (AIV) and IBV (Barjesteh et al., 2020). The fight against infectious diseases, particularly IBV, has become a research challenge that aims to develop effective remedies to mitigate their effects and thus limit their spread (Fellahi et al., 2015).
IBV is a highly contagious respiratory tract virus of poultry, that belongs to the Coronaviridae family, and which causes morbidity, mortality, and reduced feed conversion, leading to considerable damage in the poultry industry (Cavanagh, 2005). Coronaviruses replicate in the cytoplasm of infected cells and have a genome of approximately 27-32 kb. Virions contain four structural proteins: the spike (S), the membrane (M), the envelope (E), and the nucleo-protein (N) (Siddell, 1994; Lai and Cavanagh, 1997; Britton et al., 2005; Casais et al., 2005; Ren et al., 2009). The IBV genome, which has the gene order replicase-S-3-M-5-N, contains two non-structural genes, 3 and 5, that express three (3a, 3b, and 3c) and two (5a and 5b) small gene products, respectively (Casais et al., 2005).
Mutation and genetic recombination result in various strains, such as the Massachusetts type (Mass.), the Arkansas type (Ark.), or the 793B type (4/91). A report established by Jungherr and his colleagues in 1956 showed the absence of cross-protection between Massachusetts (discovered in 1941) and Connecticut (discovered in 1951) pathogenic strains; this was proof of the existence of several IBV serotypes (Cavanagh and Naqi, 2003). On this basis, it is established that vaccination is the key preventive measure for countering infectious bronchitis (IB). Its application in most chicken farms has decreased large-scale outbreaks of IB (Ren et al., 2009), but live attenuated vaccines used for preventing this viral infection give little immunity against cross-serotypes (Cavanagh, 2005; Gelb et al., 2005; Liu et al., 2006). Indeed, the frequency of IBV serotype mutations makes vaccines partially effective against different strains (Zhang et al., 2022). Although the chicken’s innate responses eliminate invading viruses or allow the adaptive immune system to establish an effective antiviral response, viruses are multifactorial and complex (Barjesteh et al., 2020).
While vaccination remains the mean used to prevent diseases and fight against infections, known to be very active in certain countries, the antigenic variation between strains of the virus poses a challenge to their identification, which explains the failure of some vaccines against the infection. Indeed, cross-protection between strains is highly variable, and the emergence of new strains is a serious issue, as the protection offered by vaccines also varies (Brochu Morin et al., 2018; Regragui et al., 2025).
Currently, no antiviral drugs to treat IBV are commercialized, and farmers still rely on proper husbandry practices and available vaccines, live-attenuated and inactivated, to prevent the virus from spreading. However, despite protocols in place to control IBV outbreaks, farms still record high mortality and morbidity rates, prompting researchers to seek other solutions and alternatives for IBV treatment. Several studies have focused on the search for new natural substances allowing the control of IBV, due to their perceived advantages. These include their safety, synergistic effects, and cost-effectiveness, making them sustainable resources compared to synthetic drugs. Historically, traditional medicine relied on natural products to treat various diseases, including viral infections, suggesting that these substances may be effective in IBV infections.
The objective of this review is to gather and compare information on natural extracts and active compounds with antiviral bioactivity and establish a comprehensive description based on performance and efficacy, methods of extraction or synthesis, the active agent involved, availability of raw material, ease of large-scale application, and possibly the cost of its use. This review summarizes existing research and offers a comprehensive overview by identifying literature gaps and suggesting directions for future research.
METHOD
The selected articles for this synthesis were classified by the chronology of publication. Their results highlight the effectiveness of therapeutic agents against IBV, in particular, the active principles extracted from plants, derived either through organic synthesis or by distillation. The agents are designated by plant extract, vegetable essential oils, or mixtures.
The search was conducted using PubMed (www.ncbi.nlm.nih.gov/pubmed/) and Google Scholar (https://scholar.google.com/) databases. The following keywords were used: (coronavirus, avian and IBV) and (natural treatments, extracts, essential oils, plants, and herbal medicine). The selected articles focused on the antiviral activity of different plant parts and essential oils. Only articles up to and including 2024 were considered, and the selection of these articles was based on relevance, with a focus on recent and up-to-date studies, and methodology, meaning articles with a comprehensive overview, clinical trials, field studies, and indeed, efficacy.
RESULTS
Antiviral activity of plant extracts
Garlic, Allium sativum
Allium sativum, from the Liliaceae family, has been widely used for thousands of years for its medicinal properties. It has been recognized for its potential to inhibit different strains of bacteria, fungi, and viruses (Singh and Singh, 2008). A. sativum has been extensively studied , in animal and human clinical trials, and in epidemiological evaluations for its multiple medicinal effects. The medicinal part of the plant is the garlic bulb, used, fresh, dehydrated, or steam-distilled oil (Tattelman, 2005).
A. sativum oil has antitumor, antioxidant, and antimicrobial properties against gram-positive and gram-negative bacteria, such as Salmonella typhimurium and Escherichia coli (Singh and Singh, 2008).
The effect of A. sativum was evaluated by performing an experiment on Specific Pathogen Free (SPF) embryonated eggs inoculated with aqueous A. sativum extract and two strains of IBV, 4/91 (acute) being the vaccine strain and M41 (subacute) the field strain. Groups inoculated with A. sativum extract 8 hours after exposure to IBV were evaluated to determine the phase of infection during which the A. Sativum affects the virus. The results indicated that A. sativum extract may affect the virus in the replication phase. It appears from this study that A. sativum extract has variable effects, with greater efficacy on sub-acute strains. However, as a treatment after exposure to the virus, the effect is significant on both sub-acute and acute strains, as it has reduced the mean embryo index (EI) in both strains, with p-values<0.5, showing statistical significance (Table 1) (Mohajer Shojai et al., 2016).
The round tiger nut, Cyperus rotundus L.
Cyperus rotundus L. of the Cyperaceae family is considered a noxious weed to crops but is valued for its therapeutic effects, including anti-inflammatory, antimicrobial, antioxidant, antidiabetic, and antispasmodic properties (Singh et al., 2016). The parts of C. rotundus used are its tuber, leaves, seeds, rhizomes, and oil, as they contain the major active components: flavonoids, terpenoids, and essential oil (Das et al., 2015).
A recent study combined the aqueous extract of the roots of C. rotundus L. and silver nitrate (AgNO3) to synthesize green silver nanoparticles (Figure 1). After determining the maximum nontoxic concentration (MNTC) by microscopically observing Vero cells’ morphology 12 hours post-incubation, Vero cells were exposed to different concentrations of the aqueous extract and the corresponding nanoparticles before and following infection. The results showed antiviral activity of green silver nanoparticles in both pre-exposure and post-exposure cases to IBV (undetermined strain). However, the antiviral effect was greater for treated cells after virus infection (Figure 2). This study suggested an interaction of C. rotundus nanoparticles with the proteins of the outer envelope of IBV (Abo-El-Yazid et al., 2022).
Weeping Forsythia, Forsythia suspensa Vahl
Forsythia suspensa Vahl, from the Oleaceae family, is a shrub native to China whose fruits have been widely used in Asia for treating gonorrhea, erysipelas, inflammations, pyrexia, and ulcers. Its leaves have also been added to tea as a nutritional supplement (Qu et al., 2010). F. suspensa has both antibacterial and antioxidant activities. A 2007 study also demonstrated the antibacterial and antioxidant activities due to its compounds forsythiaside (forsythoside-A) and forsythine (Qu et al., 2008).
The antiviral activity of forsythoside A against the M41 and Beaudette field strains of IBV has been evaluated in vitro in chicken embryo kidney (CEK) cells and baby hamster kidney (BHK) cells, as well as in vivo on chicken. In CEK cell cultures, results showed that treatment before infection inhibited the production of IBV. In addition, the antiviral effect was confirmed by real-time RT-PCR. However, when administered after infection, forsythoside-A did not decrease the infectivity of the virus. These results prove that forsythoside-A inhibits IBV infection in vitro in a dose-dependent manner (Li et al., 2011).
On BHK cell cultures, pretreatment with forsythoside A inhibited IBV replication in a dose-dependent way and reduced inflammation, apoptosis, and autophagy induced by the viral infection (Xu et al., 2023). A 2020 in vivo study demonstrated both respiratory symptoms and activities of IBV-infected chickens were improved following forsythoside-A treatment (Wang et al., 2021). Furthermore, a synergistic effect of phylligenin and baicalin, extracted from F. suspensa and Scutellaria baicalensis, respectively, have proven to be effective against IBV by improving respiratory tract flora and metabolic disorder in broilers (Table 2) (Feng et al., 2024).
Chinese skullcap, Scutellaria baicalensis
Scutellaria baicalensis, a flowering plant from the Lamiaceae family, has been famous in traditional medicine. Its roots were known for their numerous pharmacological properties, including antioxidant, antiviral, and antimicrobial effects (Zhao et al., 2016). One of its main active compounds is baicalin, a flavonoid used to prevent IBV infection. In addition to its synergistic effect with phylligenin (extract of F. suspensa) against IBV (Feng et al., 2024), a recent study tested its efficacity on a nephropathogenic strain (NIBV) in vivo. IBV-infected chicken treated intranasally with 10 mg/kg of baicalin showed improved spleen health and alleviation of NIBV infections overall. Specifically, baicalin inhibited mitophagy induction and promoted innate immunity by activating type 1 IFN response (Tian et al., 2023).
Chinese pepper, Houttuynia cordata
Hottuynia cordata is an herbaceous plant of the Saururaceae family, rich in oil, flavonoids, and alkaloids (Bauer et al., 1996). Pharmacological studies have indicated that the components of the essential oil of H. cordata possess anti-inflammatory, antibacterial, and antiviral activities. Furthermore, flavonoids had antineoplastic, antioxidant, and antimutagenic effects, while alkaloids were proven to have potent antiplatelet and cytotoxic properties (Fu et al., 2013).
The inhibitory effect of H. cordata on Beaudette and HH06 IBV strains was achieved by using its essential oil with sodium chloride solution (Yin et al., 2011). As the Beaudette strain didn’t cause any mortality, the HH06 IBV strain was used in all experiments (Table 3). In vitro, the mixture showed equal efficacy on Vero and CEK cells. RT-PCR analysis targeting the S1 gene suggested partial inactivation of the virus. In ovo, H. cordata prevented embryo mortality of SPF eggs, and in vivo, the virus had lower infectivity in chickens but did not provide complete protection. Likewise, using in vitro test, H. cordata failed to protect virus-infected cells. As a result, H. cordata can be combined with other drugs or vaccines to get a better result (Yin et al., 2011).
Perforated St. John’s Wort, Hypericum perforatum
Hypericum perforatum is an angiosperm plant of the Clusiaceae family. The main active constituents are hyperforin and hypericin (Barnes et al., 2001). Several pharmacological activities have been documented, including wound healing and antimalarial effects, as well as antioxidant, anticancer, antiviral, antibacterial, and antifungal properties. St. John’s Wort is also used to treat psychosomatic disorders, seizures, depression, dementia, and anxiety (Velingkar et al., 2017; Mullaicharam and Halligudi, 2018).
The predominant phytochemicals of H. perforatum are synthesized and stored in glands and secretory pockets located at the level of its aerial parts and are accumulated exclusively in the flowers (Patočka, 2003; Velingkar et al., 2017).
The antiviral activity of H. perforatum on the M41 field IBV strain was evaluated using ethyl acetate extract. In vitro testing on CEK cells showed a dose-dependent reduction in viral mRNA levels following treatment with the ethyl acetate extract and inhibition of IBV-induced apoptosis. In vivo, the infected group treated with a gradual increase in extract dose showed decreased excretion of tracheal cilia and epithelial cells and reduced inflammatory serous fluid exudation. Results revealed fewer inflammatory cells and erythrocytes and reduced mRNA expression levels in the trachea and kidneys of chicks treated with ethyl acetate. Therefore, the extract from H. perforatum has a strong antiviral effect on IBV (Chen et al., 2019). Another study investigating the activity of hypericin on the M41 IBV strain in CEK cells inhibited the virus-induced apostosis and reduced reactive oxygen species (ROS) generation induced by IBV (Table 4) (Chen et al., 2019).
Ginseng, Panax ginseng
Panax ginseng is a Korean plant from the Araliaceae family. The main active ingredients of P. ginseng are the ginsenosides extracted from the roots, leaves, and flowers (Gillis, 1997). The pharmacological effects are improvement of brain functions, inhibition of pain, prevention of cancer, and strengthening of the immune system (Choi, 2008).
The therapeutic activity of P. ginseng against the H120 vaccine strain was evaluated in chickens by combining ginseng stem-leaf saponins (GSLS) with selenium (Se) and administrating it as an adjuvant to the vaccine (Ma et al., 2019). The results showed a strengthening of the immune response through rapid and lasting production of antibodies, proliferation of lymphocytes and cytokines in the blood, and a rise of neutralizing antibodies (Ma et al., 2019).
Cholistani Plants
Different plants native to the Cholistan desert in Pakistan are renowned for their medicinal benefits, including their antiviral effect, especially against IBV. These plant species include Oxystelma esculentum, Achyranthes aspera, Salsola baryosma, Neuroda procumbens, and Ochthochloa compressa (Aslam et al., 2010) (Shahzad et al., 2020).
The antiviral effects of Cholistani Plants were tested against IBV using different extracts, namely n-hexane, ethyl acetate, and n-butanol extracts. The results showed that 5 n-hexane extracts out of 11, 10 ethyl acetate extracts out of 11, and 5 n-butanol extracts out of 11 were active against IBV. O. esculentum, A. aspera, S. baryosma, N. procumbens, and O. compressa are the five plants whose extracts were effective in controlling IBV (Table 5) (Figure 3) (Shahzad et al., 2020).
Elderberry, Sambucus nigra
Sambucus nigra L., a shrub in the family Adoxaceae, is recognized for its antioxidant, anti-inflammatory, antiallergic, antiviral, anti-urolithiasis, and antidiabetic pharmacological effects. All parts of the plant (flowers, fruits, leaves, bark, and roots) proved effective. However, the most commonly used parts are the flowers and fruits, which are included in the composition of many food products and pharmaceutical and cosmetic preparations (Młynarczyk and Walkowiak-Tomczak, 2017).
S. nigra is known for its antiviral activity against influenza A and B viruses. Treatment of IBV Beaudette strain in Vero cells with the extract of S. nigra at an early stage of infection inhibited the virus. Observation by electron microscopy revealed that the extract of S. nigra disrupts the structure of the IBV virion, as compromised envelopes and the presence of membrane vesicles were observed, likely rendering it non-infectious. The hypothesis is that the polyphenols, with antiviral properties, present at high levels in the plant are the source of this inhibition (Chen et al., 2014).
Enantia chlorantha
Enantia chlorantha is a high tree mainly found in tropical Africa (Cameroon, Gabon, and Congo) and undergrowth of the rainforest from the south of Nigeria to Angola. Palmatine, the main component of the protoberberine extract from this tree, is a natural non-flavonoid alkaloid that has proven effective against IBV. In vitro, palmatine inactivated IBV (undetermined strain). It inhibited the adsorption, penetration, and intracellular replication in CEK cells by increasing pro-inflammatory cytokines IL-1β and TNF-α expressions and inducing type 1 interferon production (Figure 4) (Zhang et al., 2024).
Mixed Herbal Extract
Certain plants of the families Myricaceae, Pinaceae, Primulaceae, Polygonaceae, and Anacardiaceae naturally contain a flavonoid, myricetin, that has various pharmacological powers: antioxidant, antiviral, antibacterial, anticancer, and anti-inflammatory (Agraharam et al., 2022).
After treating IBV-infected Vero cells (undetermined strain) with myricetin, the duration of expression of the antiviral effect in these cells was shorter than in virus-infected not-treated cells, which means that the myricetin may play a role in inhibiting the immune evasion mechanism of IBV and enhancing the innate immune response against IBV infection. The results showed that myricetin targeted the Papain-Like protease (PLpro) of IBV by inhibiting the deubiquitination of its activity and modulating NF- κB and IRF7 pathways (Peng et al., 2022).
Antiviral activity of mixtures
The mixtures are blends of plant extracts of different natures, natural active ingredients, essences, or essential oils which have therapeutic properties for controlling IBV.
Mixture AuraShield L
AuraShield L is a blend of citrus extract, maltodextrin, sodium chloride, lactic acid, and citric acid. The in vitro experiment was conducted in Hep-2 cells using the B1648 IBV strain. Pretreatment with AuraShield L reduced plaque count by over 80%, while post-treatment led to a 52% reduction in virus titer. The in vivo experiment in chickens using the same strain showed the AuraShield L mixture inclusion in drinking water reduced viral load in the trachea and lungs of broiler chickens by more than 80%. It also reduced clinical signs, such as rales, sneezing, coughing, and dyspnea, registering a 93.7% survival rate in the treated group vs. 66.6% in the untreated one. The mechanism of action might involve an increase in IgA levels and short-chain fatty acid production in both the trachea and lungs (Balta et al., 2020).
Mixture QR448(a)
QR448(a) is an antiviral product composed of a mixture of oleoresins and essential plant oils (produced by Quigley Pharma, 2008), recommended for the transmission prevention of IBV in chickens.
The effect of QR448(a) on IBV was tested in vitro in Vero cell culture and embryonated eggs using the Beaudette strain and in chickens using the M41 and Ark. strains (Jackwood et al., 2010).
For Vero cell culture, the minimum dose against the Beaudette strain of IBV was 1 × 103 at 1 × 100,8 TCID50/ml.
In vivo experiences in IBV-infected chickens showed the efficacy of administering QR448(a) by intranasal inoculation and spraying two hours before the challenge, whereas water administration had little effect regardless of the treatment period. Therefore, QR448(a) reduced IBV titer below an infectious threshold (Jackwood et al., 2010).
Treatment with QR448(a) protected chickens up to 4 days after treatment from the expression of clinical signs of disease, but not against infection, and reduced IBV transmission over 14 days, as stated by Quigley Pharma.
QR488(a)-induced transmission reduction could control the spread of IBV in the herd and likely decrease or prevent the persistence of the Arkansas virus. Since QR448(a) is effective against the pathogenic M41 strain of IBV, it may also limit the transmission of field pathogenic strains of IBV in commercial broilers (Jackwood et al., 2010).
Antiviral activity of essential oils
Essential oils are a complex mixture of volatile organic compounds naturally synthesized by plants and extracted through low-pressure steam distillation. Their structure includes a range of chemical compounds, including phenolics, terpenoids, aldehydes, ketones, ethers, and epoxides. These components confer efficacy against bacterial, fungal, and viral pathogens, as well as the potential to enhance the immune system (Zhang et al., 2022).
Mixture of Cinnamaldehyde and Glycerol Monolaurate
The antiviral effect against IBV in vivo of a mixture of cinnamaldehyde (CA) extracted from cinnamon and glycerol monolaurate (GML) extracted from coconut oil was studied by Zhang et al. (2022). The choice of these compounds was due to their documented antiviral properties. Among the virtues of CA is its beneficial effect on nutrition, metabolism, and growth of broilers and enhancement of their immune function (Bravo et al., 2011). On the other hand, GML is a natural compound considered a safe and effective alternative to antibiotics; it promotes growth and has antimicrobial, antiviral, and anti-inflammatory properties (Bravo et al., 2011; Minjie Zhao et al., 2020).
The experiment used broiler chickens to evaluate the effectiveness of the mixture of plant essential oils (PEO) made of CA and GML in vivo (Figure 5). All the groups received nasal-ocular 108 50% tracheal organ culture infection dose (TOC-ID50), except the blank group (uninfected and untreated). Results relating to antiviral therapy against the M41 IBV strain showed out of three doses tested (PEO-L: 0.5 ml/l; PEO-M:1 ml/l and PEO-H: 2 ml/l), 1ml/l registered the highest cure rate of 92.3%, reduced symptoms in chickens and decreased mRNA expression levels and IL-6 levels, while increasing IL-4 and IFN-γ anti-inflammatory factors. Therefore, the mixture of CA and GML could significantly inhibit viral proliferation and improve immune function for a dose of 1 ml/l in drinking water in chickens (Zhang et al., 2022).
Mixture of L-menthol and cineole
The therapeutic actions of essential oils on respiratory infection in broiler chickens were tested by Barbour et al. (2008), using a mixture of eucalyptus and peppermint essential oils.
Its active ingredient, 1,8-cineol, known as eucalyptol, is used to reduce respiratory infections of viral or bacterial origin (Barbour et al., 2008).
Eucalyptus spp. of the Myrtaceae family is an aromatic tree native to Australia with wide adaptation, particularly Eucalyptus globulus, a species introduced to multiple environments for the production of paper pulp, notably in Europe around the Mediterranean, in North Africa, and Latin America. A study on the chemical composition of the essential oils of eight species of eucalyptus, as well as the evaluation of their antibacterial, antifungal, and antiviral activities, showed that the species E. cinerea is the richest in 1,8-cineol and that its antimicrobial activity is the highest (Elaissi et al., 2012).
Eucalyptus is toxic to humans and animals in general. It contains cyanogenic glycosides that can release hydrocyanic acid and block cellular respiration (Gleadow and Møller, 2014). However, cineole eucalyptus oil is safe for adults; systemic toxicity may result from ingestion or topical application of quantities above recommended doses (Darben et al., 2007).
Mentha piperita is an aromatic plant from the Lamiaceae family. The leaves are generally destined for culinary purposes, while the essential oil is used to flavor confectionery, toothpaste, and medicine. Pure peppermint oil is almost colorless and is rich in menthol.
The mixture of L-menthol and cineole was administered to immuno-compromised broiler chickens exposed to Mycoplasma gallisepticum, the live strains B1 and LaSota Newcastle of the vaccine against the disease, the virus infectious bursal disease and Mass. IBV strain. The obtained results showed that this mixture was able to reduce morbidity 2 days after the IBV challenge and to reduce specific lesions such as abdominal airsacculitis, enteritis, splenomegaly, bursal congestion, and liver hypertrophy (Barbour et al., 2008). The effective dose for IBV treatment was 0.25 ml/l of drinking water. In addition, treatment with this mixture improved the feed consumption index and the conversion coefficient (Barbour et al., 2008).
DISCUSSION
In the articles consulted, the plants used are frequently native species, which gives the therapeutic trials a regional character specific to the strains of IBV identified locally. Other plants are cosmopolitan species whose tests are more extended geographically. Also, many plant-derived antiviral compounds have been, fully or partially, characterized as bioactive compounds, able to directly or indirectly reduce viral bronchial infection in vitro or in vivo. The most commonly used test methods to assess IBV infectivity include cell viability assays and quantitative RT-PCR.
Our review focused on the action of plants against IBV strains, emphasizing the most significant mechanisms of action. The modes of action that emerged from our review showed that plants such as A. sativum and coconut oil extract (GML) were effective during the replication phase. Others, however, affected the virus envelope, either by altering its proteins or by inactivating or disrupting the viral membrane, such as C. rotondus, S. nigra, or the QR448 mixture. P. ginseng, F. suspense, and H. perforatum, as well as the Aurashield blend targeted lymphocytes and reduced pro-inflammatory cytokines levels. Myricetin inhibited the deubiquitinating activity of the papain-like protease, restoring the ubiquitin modification and promoting an innate response.
The molecular mechanisms of some natural products against IBV have been partially elucidated, while for others, they remain unknown. The variety of research protocols has made comparing results across studies challenging. Furthermore, in vitro results do not always translate to in vivo effectiveness because of variations in metabolism, absorption, and immune responses. In vivo experiments also face challenges due to the lack of mechanism insights, the influence of health conditions, and the route of treatment administration, all of which can affect absorption. Notably, recent in ovo experiments using thymoquinone—a bioactive compound extracted from Nigella sativa—demonstrated significant antiviral activity against IBV, supporting its potential as a natural antiviral agent (Regragui et al., 2025). These findings contribute to the growing body of evidence highlighting the efficacy of plant-derived compounds in controlling IBV infections in vivo.
Some experiments used field strains, mainly the M41, while others used vaccine strains, such as H120 and 4/91. Vaccine strains are attenuated or inactivated versions of the pathogen and using them in a controlled setting decreases the risk of causing an outbreak. Because vaccine strains are standardized, their consistency reduces variability in results and ensures reproducibility across different studies and laboratories. On the other hand, using field strains in experimentation provides real-world relevance. It also allows researchers to evaluate products’ effectiveness against a wide range of viral variants present in the field. Experimenting with field strains ensures realistic outcomes, as researchers can predict how the treatment will act on viruses circulating in the field, thus finding practical solutions and a better understanding of the effectiveness of treatments in natural environments.
While testing various antiviral natural products may seem advantageous, the variability in their composition could lead to inconsistent results. Factors such as the source and geography of the plant change active compound levels and influence biochemical profiles. Moreover, the extraction methods of active components from plants can affect their composition. Due to this inherent variability, achieving standardized protocols proved complicated, making it challenging to draw reliable conclusions about their efficacy.
This variability has also been observed in antibacterial studies using essential oils, such as those derived from cinnamon and oregano, which showed significant effects against avian Escherichia coli strains (Khribch et al., 2018).
Similarly, essential oils from plants like Plectranthus amboinicus have demonstrated antimicrobial potential, reinforcing the interest in natural substances for managing infectious diseases in poultry (Hassani et al., 2012).
However, all the studies showing efficacy against IBV provided a strong basis for implementing strategies against all coronaviruses, as natural products used to reduce respiratory inflammation caused by IBV or to modulate the immune response could yield promising results in managing Sars-CoV-2 infections and addressing the virus complications.
CONCLUSION
It emerges from this research that certain plants tested revealed promising properties against strains of IBV, particularly the inhibiting action of the infection by their different extracts. The results from this synthesis confirm the importance of plant selection for the adjustment of their bioactivity according to a set of criteria: i) Plant availability; ii) Adequate technique for extraction of the active ingredient; iii) Identification of bioactive molecules and the stage of their antiviral performance and iv) Potential and cost of their large-scale application. However, the lack of statistical analysis in many studies prevents drawing conclusive results about the efficacy of natural products, and remedying this requires more thorough research. That is why establishing standardized protocols that ensure repeatability and reproducibility is essential for having reliable findings.
Therefore, the application of a therapeutic protocol highlighting these active substances, or the possibility of combining them and using them as adjuvants, proves to be a necessary and promising alternative for broad efficacy against IBV. With further research, these results could be extrapolated to other coronaviruses, especially human ones such as MERS-CoV, SARS-CoV, and COVID-19.
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