In recent years, viral infections have emerged as major global public health concerns, with increasing incidence and geographic spread. These infections significantly impact global health and economies due to their epidemic and pandemic potential (1). RNA viruses, in particular, are leading causes of human infectious diseases. Their high mutation rates contribute to the emergence of new viral subtypes and genotypes resistant to existing therapies, posing persistent threats of new outbreaks (2). For instance, Influenza A virus (H1N1), an enveloped, single-stranded RNA virus of the Orthomyxoviridae family, is responsible for most seasonal influenza epidemics (3). Highly pathogenic avian influenza A (H5N1) has also caused recent outbreaks involving zoonotic transmission (4). Similarly, SARS-CoV-2, a member of the Coronaviridae family with a single-stranded RNA genome encoding approximately 29 proteins, caused the COVID-19 pandemic, resulting in over seven million deaths worldwide (5). Although licensed antiviral therapies exist, RNA viruses can rapidly evolve through reassortment and point mutations, leading to resistance against conventional treatments such as neuraminidase inhibitors for Influenza (6) and protease inhibitors targeting SARS-CoV-2 main protease (M^pro) (7).

In addition, four arboviruses Dengue (DENV) and Zika (ZIKV) (Flaviridae family), as well as Chikungunya (CHIKV) and Mayaro (MAYV) (Togaviridae family) primarily transmitted by the mosquito Aedes aegypti or Haemagogus janthinomys (MAYV), are single-stranded RNA representing a significant global public health concern, particularly due to their increasing geographic distribution and potential to cause a wide spectrum of neurological complications in recent years (8). Dengue virus, with its four major serotypes (DEN-1 to DEN-4), infects up to 400 million people annually (9, 10). Although vaccines and therapeutics are available, their efficacy varies widely across serotypes (11). No effective treatments or vaccines currently exist for Zika virus, Chikungunya virus, or Mayaro virus, highlighting the urgent need for new antiviral agents. Therefore, identifying new inhibitors for these arboviruses is imperative. With over 42.3 million deaths reported over the past four decades, HIV continues to affect global populations. Its single-stranded RNA genome encodes 15 proteins essential for viral replication and immune evasion. While antiretroviral therapies have significantly reduced viral loads, they are not curative and often cause adverse side effects. A prophylactic vaccine is still lacking (12).

This scenario raises an intensified focus on medicinal plants since they hold an immense reservoir of bioactive compounds that could lead to the discovering novel antiviral drugs (6, 13). Such compounds include mainly diverse secondary metabolites, isolated, purified, and identified from the crude extracts of various plant parts, harboring rich structural and chemical diversity which allows them to interact with different biological and viral targets (7). These characteristics led to wide functionality of these phytochemicals, favoring a sustained safety and effectiveness blocking multiples viral infections (14, 15). This review presents recent advances in plant-derived extracts and phytochemicals that inhibit various stages of the viral life cycle of Influenza, Dengue, Zika, Chikungunya, Mayaro, Coronavirus, and HIV ( Figure 1 ), underscoring their potential for antiviral drug development.

Here we analyze 17 extracts and 16 isolated compounds from species across 12 plant families that exhibit anti-influenza activity, as listed in Table 1 .

For instance, dry extracts from the aerial parts of Spiraea species have demonstrated a pronounced antioxidant effect against Influenza A, as well as cytoprotective activity by reducing the viral cytopathic effect in infected cells (41). Accordingly, the hydroethanolic extract of Caesalpinia mimosoides, primarily containing flavonoids and glycosylated derivatives, showed strong antioxidant and antiviral properties against H1N1. In this context, computational molecular docking studies revealed that multiple derivative metabolites preferentially interacted with viral neuraminidase and the PB2 subunit of RNA polymerase, suggesting potential mechanisms of anti-influenza activity. Molecular dynamics simulations and further in vitro assays are needed to support its therapeutic potential (32). Similarly, Melk (2024) (16) reported that hydroethanolic extracts of Ruellia tuberosa and Ruellia patula, both rich in flavonoids, exhibited antiviral activity against H1N1 by reducing infectious viral particles, likely through molecular interactions between the bioactive compounds quercetin, hesperetin, and rutin with viral neuraminidase (NA), as determined by molecular docking and dynamics simulations. In addition, aqueous extracts of raw Nepeta cataria and Glechoma hederacea showed strong inhibitory effects on H5N1 virus replication. Specifically, the aerial parts of N. cataria were rich in catechin flavonoids, suggesting that this group of phenolic compounds may be responsible for the observed antiviral effects (30).

The butanolic extract of Davallia mariesii, a species used in traditional Chinese medicine for treating osteoporosis and inflammatory conditions, impaired the neuraminidase activity of H1N1 (26). Similarly, butanol extracts of S. glycycarpa and S. sarmentosa inhibited the replication of Influenza H1N1 (42).

A phytochemical investigation revealed that various extracts and fractions of Tilia platyphyllos, Camellia sinensis, and Myrtus communis exhibited in vitro hemagglutination inhibition after H1N1 treatment, possibly due to reduced physical interaction between the extracts and fractions and the virus surface hemagglutinin glycoprotein (36). Finally, Lonicera japonica has been studied for its antiviral properties against H1N1, using extracts from its dry buds and flowers, which are rich in acidic flavonoids. In vivo studies showed that mice treated with 600 mg/kg/day of the acidic extracts for 8 days were protected from influenza-induced death (22).

In a bio-guided assay of the ethanolic extract of Angelica dahurica, four isolated furanocoumarin compounds, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, and imperatorin, exhibited activity against both H1N1 and H9N2 viruses by inhibiting infection and replication. Notably, oxypeucedanin strongly inhibited H1N1 neuraminidase activity, suppressed the synthesis of NA and nucleoprotein (NP), and exerted an anti-apoptotic effect on virus-infected cells, suggesting multiple roles in preventing H1N1 infection and replication (63).

From the roots of Isatis indigotica, several glucosinolate compounds, epiprogoitrin, progoitrin, epigoitrin, and goitrin, were isolated, showing potent anti-H1N1 activity by interfering with viral adsorption or budding from host cells. However, mechanistic studies indicated that these glucosinolates have limited inhibitory effects on hemagglutinin and neuraminidase (53).

Other studies have shown that berberine, an isoquinoline alkaloid from Berberis vulgaris, blocks the host mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) signaling pathway, which is essential for the transport of viral ribonucleoproteins into the cytoplasm, thereby inhibiting H1N1 replication (52).

From Elaeocarpus sylvestris (Lour.), distributed in the subtropical regions of Jeju Island (Korea), Japan, and southern China, two polyphenol compounds, 1,2,3,4,6-penta-O-galloyl-β-D-glucose and geraniin, were isolated from the butanol fraction. These compounds significantly inhibited the production of H1N1 RNAs, non-structural proteins, and infectious viral particles in vitro. They also reduced pulmonary viral load and inflammatory cytokines (IFN-γ, TNF-α, and IL-6) in vivo, which are associated with disease severity in influenza infection (57).

Additionally, Camellia sinensis is a promising medicinal source, as its isolated polyphenolic compounds, theaflavins, inhibited both hemagglutinin and neuraminidase of H1N1, exhibiting a virucidal action and indicating a direct effect on the viral particle (62).

In this study, we investigated 15 species from 12 plant families, along with 9 extracts ( Table 1 ), exhibiting promising medicinal properties against Coronavirus and SARS-CoV-2.

Using UPLC-MS/MS coupled with in vitro studies and chemometric analysis, Darwish (2022) (43) demonstrated that ethanol extracts from the flowers and leaves of Lantana camara, native to the tropical regions of the Americas (cultivar Chelsea Gem), and flower extracts from the cultivars Spreading Sunset and Drap d’Or, exhibited robust selectivity indices by inhibiting the expression levels of the viral RNA-dependent RNA polymerase (RdRp) gene. These findings indicate high safety, efficacy, and promising anti-COVID-19 properties. Additionally, in vitro tests were conducted to assess the crude methanolic leaf extract of Byrsonima coccolobifolia against SARS-CoV-2. The extract demonstrated excellent in vitro activity with no cytotoxicity under the tested conditions, confirming its efficacy and safety against SARS-CoV-2 (35).

In a study by Giugliano (2024) (39), ethanolic extracts of Moringa oleifera leaves obtained via microwave-assisted extraction showed significant inhibition of coronavirus HCoV-229E infection, without cytotoxic effects in either of the two cell models used.

Likewise, the methanolic extract of Strobilanthes cusia leaves, traditionally used in Chinese medicine for respiratory viral infections, potently inhibited the cytopathic effect (CPE) and viral RNA yield of human coronavirus NL63 (HCoV-NL63), indicating potential to block viral infection and replication (17). Similarly, antiviral activity was observed with the methanolic extract of Ficus rubiginosa leaves against coronavirus HCoV-229E by impairing viral replication (38).

Azadirachta indica and Melia azedarach, both long used in traditional Indian folk medicine, had total methanolic extracts enriched with phenolic and flavonoid compounds evaluated against SARS-CoV-2. These showed strong antiviral activity and robust safety indices by restraining infectious viral particles (37). Likewise, the methanolic extract of Strychnos mattogrossensis was reported for the first time to have biological activity against SARS-CoV-2, protecting cells from the virus’s cytopathic effects (34). Additionally, methanolic leaf extracts of Vitis vinifera significantly reduced SARS-CoV-2 replication at early stages of infection by directly blocking expression of the spike protein, as confirmed by Real-Time PCR (44). Similarly, Cistus ladanifer, a traditional Moroccan medicinal plant, was shown by Bouothmany (2025) (24) to interfere with both replication and viral entry into SARS-CoV-2-infected host cells. Ethyl acetate and dichloromethane extracts of its leaves were particularly effective against the Omicron variant.

Melissa officinalis, with a long history of use in Mediterranean and Western Asia, showed strong virucidal and antiviral activity in its methanolic extract by inhibiting SARS-CoV-2 infection, with a robust safety profile (selectivity index of 230). The inhibition mechanisms of five key compounds from M. officinalis were investigated via molecular docking, revealing strong binding affinities with the spike receptor-binding domain (RBD) of SARS-CoV-2, indicating promising anti-infective action (29).

Numerous studies have evaluated the ability of isolated natural compounds to inhibit viral replication by targeting M^pro and PL^pro of SARS-CoV-2. For example, the alkaloids vasicoline, vasicolinone, vasicinone, vasicine, adhatodine, and anisotine, particularly enriched in the leaves of Justicia adhatoda, were examined using molecular docking, dynamics simulations, and molecular mechanics with Generalized Born surface area (MMGBSA) calculations. Notably, anisotine was more effective at inhibiting M^pro than the approved antiviral drugs darunavir and lopinavir, suggesting its potential to block SARS-CoV-2 replication by inhibiting M^pro enzymatic activity (46). Sesquiterpene metabolites claroguaiane A, claroguaianes B and C, and claroeudesmane A, derived from Carpesium abrotanoides (native to Europe, Japan, and the Himalayas), were tested via bio-guided inhibitory activity assay against SARS-CoV-2 M^pro. Claroeudesmane A showed moderate activity, while 1β-hydroxy-8-epi-inuviscolide demonstrated stronger activity. Other compounds showed no noticeable effect (50). Srinivasan (2022) (51) evaluated phenolic compounds for PL^pro inhibition. In vitro and structural assays showed that 4-hydroxybenzaldehyde (from Tagetes patula), 3,4-dihydroxybenzoate (from Acalypha torta), and 4-(2-hydroxyethyl)phenol (from Lawsonia alba) effectively inhibited PL^pro under non-cytotoxic conditions.

Natural compounds may also prevent SARS-CoV-2 infection. Kuwanon C, a flavone from Morus alba, was shown by Kim et al. (2022) (58) to suppress SARS-CoV-2 cell entry. ELISA and in vitro kinetic binding analysis confirmed that kuwanon C effectively blocked spike S1 RBD-ACE2 interaction. In silico docking simulations supported this, making kuwanon C a promising lead compound. Yang (2025) (45) reported that crude extracts from seed embryos of Nelumbo nucifera, as well as the isolated alkaloid neferine, significantly reduced SARS-CoV-2 infectious particles and showed improved virucidal activity and safety when combined with organic salts. The virucidal effect of β-escin, a bioactive constituent in Aesculus hippocastanum seed extract, was also tested. β-escin limited virus infection in vitro and reduced SARS-CoV-2 spike protein expression as seen via immunofluorescence microscopy (60).

Finally, oleandrin, a cardiac glycoside from Nerium oleander, was tested in vitro against SARS-CoV-2, significantly reducing viral replication, likely by blocking ATP binding sites on Na/K-ATPase. In vivo tests on golden Syrian hamsters treated with up to 130 µg/mL oleandrin for 7 days provided preliminary evidence of efficacy (49).

The potential therapeutic properties of plant extracts from 22 species across 17 families are explored in this section, as outlined in Table 1 .

Alagarasu (2022) (18) reported in vitro anti-Dengue and anti-Chikungunya activities of extracts from several plant species, including Plumeria alba, Ancistrocladus heyneanus, Bacopa monnieri, and Vitex negundo, commonly used in traditional medicine in Belagavi, India. Specifically, chloroform extracts of the bark of P. alba and A. heyneanus, and the hydroalcoholic extract of the whole B. monnieri plant, reduced replication or infection of Dengue and Chikungunya viruses, while the chloroform extract of V. negundo leaves showed activity only against Dengue. In addition, Ocimum sanctum, a traditional Ayurvedic herb known as Vishnu-Priya or Tulsi, containing the isolated compound eugenol (1-hydroxy-2-methoxy-4-allylbenzene), exhibited potent inhibition of Dengue-2 replication, achieving complete inhibition in in vitro assays. Docking analysis showed that eugenol interacts with Dengue non-structural proteins NS1 and NS5 with binding energies of 5.33 and 5.75 kcal/mol, respectively, suggesting potential pharmacological use in Dengue treatment (31). Jayasekara (2024) (33) investigated the antiviral potential of aqueous extracts from the roots of Glycyrrhiza glabra (Leguminosae) against Dengue and found that subfractions of the extract significantly suppressed viral adsorption to cells.

Carvalho (2023) (40) reported that methanolic and hydroalcoholic leaf extracts, as well as a methanolic bark extract from Phyllanthus brasiliensis, showed potent in vitro activity against Zika virus infection. Similarly, Chan (2021) (25) reported in vitro activity of ethyl acetate extracts of Gynura bicolor and Sechium edule against Chikungunya virus replication, and the activity of Ocimum americanum against both infection and replication of this virus.

The ethanolic leaf extract of Fridericia formosa, a Bignoniaceae species rich in xanthones and found in the Brazilian Cerrado biome, exhibited effective activity against Mayaro virus infection (20). In turn, Fridericia chica, rich in flavonoids and traditionally used in Latin American countries to treat infections, showed activity against Dengue-2, Zika, and Mayaro viruses in in vitro assays (21). Lastly (23), reported that ethyl acetate extracts of Maytenus quadrangulata leaves had a virucidal effect against Mayaro virus by acting on viral adsorption and internalization.

In this respect, pure phenolic compounds, euparin, 2-oxo-8-deoxyligustrin, and santhemoidine, isolated from Urolepis hecatantha, Stevia alpina, and Stevia satureiifolia, respectively, were able to inhibit Dengue virus infections (19). Furthermore, two major alkaloid compounds, canthin-6-one and 1-hydroxy-11-methoxycanthin-6-one, abundant in the roots of Brucea javanica, a traditional medicinal plant used in Malaysia for treating fever, showed potential binding interactions with the active sites of the NS5 protease and RNA-dependent RNA polymerase (RdRp) by molecular docking analysis using DENV-2. Notably, 1-hydroxy-11-methoxycanthin-6-one reduced viral RNA load in in vitro assays (61).

Phytochemical investigations of Crinum jagus revealed the presence of lycorine and several alkaloids from the cherylline, crinine, and galanthamine groups, which efficiently inhibited both Dengue and Zika viruses. Specifically, cherylline effectively hindered RNA synthesis in both viruses, indicating RNA replication as its main target (47). In turn, lycorine inhibited Zika RNA synthesis by binding to RdRp in vitro and protected against Zika-induced lethality by reducing viral load in vivo (48). Additionally, Phyllanthus phillyreifolius, endemic to Réunion Island and traditionally used to treat fever, venereal diseases, and kidney stones, contains the polyphenol-rich compound geraniin, which prevented RNA production in Zika-infected human cell assays (59). For Chikungunya, fractions of Humulus lupulus containing α-acids, β-acids, cohumulon, canthohumol, and flavonoids were found to affect the entire viral cycle, from entry to the egress of newly formed viral particles, without cytotoxic effects. Notably, the acylphloroglucinol β-acid fraction exhibited the strongest virucidal effect in vitro and caused a significant reduction in viral replication in drug-addition cell experiments (54).

Two species of medicinal plants and four promising isolated compounds ( Table 1 ) with anti-HIV activity are discussed in this section.

The hydroalcoholic and aqueous extracts from the roots of Withania somnifera, commonly used in traditional Indian medicine, were investigated for their bioactive potential against HIV-1 replication. In vitro enzymatic analysis revealed that the hydroalcoholic extract inhibited HIV-1 integrase activity by 86.18%, while the aqueous extract achieved 93.98% inhibition. For HIV-1 protease activity, the hydroalcoholic and aqueous extracts showed inhibition rates of 91.77% and 84.84%, respectively. Regarding HIV-1 reverse transcriptase (RT) activity, the hydroalcoholic extract exhibited 76.82% inhibition, whereas the aqueous extract demonstrated a lower inhibition rate of 58.53%. All results were obtained within the sub-cytotoxic concentration range.

Confirmatory cell-based assays showed that both hydroalcoholic and aqueous extracts effectively inhibited infectious virus release, as indicated by HIV-1 p24 detection, even at lower dosages, with EC₅₀ values of 17 µg/mL and 59 µg/mL, respectively. Additionally, in silico molecular docking studies revealed the highest binding affinity against HIV-1 integrase by the compounds 12-deoxywithastramonolide and 27-hydroxywithanone; against HIV-1 protease by ashwagandhanolide and withacoagin; and against HIV-1 reverse transcriptase by ashwagandhanolide and withanolide B. These findings suggest potential mechanisms for the inhibition of HIV-1 replication (12). Another species, Croton dichogamus, traditionally used in African medicine, exhibited significant anti-HIV activity in its methanolic extract. This extract inhibited more than 90% of infectious viral particles in cell lines (IC₅₀ value of 0.06 µg/mL) and demonstrated a high safety profile, with a selectivity index (SI) of 318.5 (27).

Anogeissus acuminata, an Asian species found in the Bandarban, Chattogram, Cox’s Bazar, Khagrachari, and Rangamati regions of Bangladesh, produces two dibenzylbutadiene lignans: anolignan A and anolignan B. Both compounds showed significant inhibitory activity against the HIV-1-RT. Furthermore, the two phytocompounds exhibited a synergistic effect against this enzyme (55). Similarly, from the leaf extract of Shepherdia argentea, the tannins shephagenin A and B were isolated and also demonstrated inhibitory activity against the HIV-1-RT, highlighting the importance of these compounds as potential HIV-1 reverse transcription inhibitors (56).

The ongoing discovery of bioactive compounds in plants represents a valuable source for identifying new, potent antiviral agents and selective compounds. These compounds not only offer potential as standalone treatments but can also complement or enhance existing therapies, especially when they exhibit synergistic interactions with other drugs. This can increase the overall effectiveness and potentially reduce adverse side effects. However, the connection between traditional knowledge and future research on plant-derived products with potential pharmacological properties should be further strengthened.

This mini-review provides an overview of recent literature (from the last five years) on medicinal plant extracts and isolated natural compounds with potential antiviral effects. A major limitation in exploring the bioactivity of plant-derived products lies in the absence of standardized methodologies for extraction, fractionation, and characterization. This is due to the immense diversity of extracts and phytochemicals found in nature, which ultimately affects the development of new antiviral agents (64). For instance, isolating alkaloid phytocompounds presents several challenges, such as solvent use, low extraction efficiency, and variations in plant genotype, all of which complicate the process of obtaining consistent yields. Moreover, the current understanding of the antiviral activity of plant-derived extracts and compounds is mainly based on in vitro studies, limiting their clinical applicability.

In this context, emerging technologies such as artificial intelligence (AI) have proven effective in predicting and optimizing the chemical, physical, and biological properties of phytocompounds. AI contributes to accelerating the identification of bioactive molecules that can target viral pathogens. Similarly, CRISPR-Cas technologies are increasingly being employed in plants to speed up the screening of phytocompounds and their targets through functional characterization. Additionally, these strategies enhance and optimize the biosynthesis of compounds in plants, offering a scalable production (65).

By applying these advanced techniques, well-characterized plant-derived compounds can be incorporated into modern medicinal chemistry. This approach could potentially alter their activity and selectivity, enabling them to target both emerging and established viral threats.