Table 1. Summary of the Last Decade’s In Vitro Data (2010-2023) on the broad-spectrum antiviral activity of the berberine Alkaloid Including 50% Maximal Effective Concentration (EC50), 50% Maximal Inhibitory Concentration (IC50), 50% Cytotoxicity Concentrations (CC50), Selectivity Index (SI), along with the Mechanism of Action and Cell Lines Used (Studies Are Listed in Chronological Order).
| Virus type | Antiviral mechanism of action | IC50 or EC50 | CC50 | SIa | Cell line | ref |
|---|---|---|---|---|---|---|
| Herpes simplex virus-1 (HSV-1) | Inhibition of viral DNA synthesis | IC50 = 0.082 (mg/mL) | 13.2 (mg/mL) | 161 | Vero E6 | (Chin et al., 2010)30 |
| HSV-2 | Inhibition of viral DNA synthesis | IC50 = 0.090 (mg/mL) | 13.2 (mg/mL) | 147 | Vero E6 | (Chin et al., 2010)30 |
| Infuenza A H1N1, (strains PR/8/34 and WS/33) | Inducting post-translationally effects in the virus life cycle to inhibit virus protein trafficking/maturation. | IC50 (strain PR/8/34) = 0.01 μM | - | - | RAW 264.7 | (Cecil, Davis, Cech, Laster, 2011)48 |
| IC50 (strain WS/33) = 0.44 μM | - | - | RAW 264.7 | |||
| Infuenza A/FM/1/47(H1N1) | Suppression of virus-induced cytopathogenic effects (CPE) and reduction of viral neuraminidase activity | IC50 (g/L) = 0.025 | 0.242 (g/L) | 9.69 | MDCK | (Wu et al., 2011)49 |
| HIV-1 NL4.3 | Inhibiting reverse transcriptase (RT) viral enzyme | EC50 = 0.13 μM | 2.09 μM | 16.07 | CEM-GFP | (Bodiwala, Sabde, Mitra, Bhutani, Singh, 2011)50 |
| HSV-1 | Suppressing HSV-induced host cell JNK and NF-kB activation, as well as disrupting early stage of the HSV-1/2 replication cycle (between viral attachment/entry and genomic DNA replication). | EC50 = 6.77 μM | >400 μM | >59.08 | HEC-1-A | (Song et al., 2014)51 |
| EC50 = 6.77 μM | 165.7 μM | 24.48 | HEK293T | |||
| HSV-2 | Suppressing HSV-induced host cell JNK and NF-kB activation, as well as disrupting early stage of the HSV-1/2 replication cycle. | EC50 = 5.04 μM | >400 μM | >79.37 | HEC-1-A | (Song et al., 2014)51 |
| EC50 = 5.04 μM | 165.7 μM | 32.88 | HEK293T | |||
| Chikungunya virus (CHIKV) | Inhibition of viral replication in a dose-dependent manner by reducing viral protein expression. | EC50 = 1.8 μM | >100 μM | >55.6 | BHK-21 | (Varghese, Kaukinen et al., 2016)52 |
| EC50 = 1.9 μM | >100 μM | >52.6 | Huh-7.5 | |||
| CHIKV | Decreased viral RNA synthesis and protein expression in a dose-dependent manner. | EC50 (strain LR2006 OPY1) = 4.5 μM | 202.6 μM | 45 | HEK-293T | (Varghese, Thaa et al., 2016)53 |
| EC50 (strain LR2006 OPY1) = 12.2 μM | 429.5 μM | 35 | HOS | |||
| EC50 (strain LR2006 OPY1) = 35.3 μM | - | - | CRL-2522 | |||
| EC50 (strain CHIKV-SGP11) = 44.2 μM | CRL-2522 | |||||
| EC50 (strain CNR20235) = 50.9 μM | CRL-2522 | |||||
| O’nyong nyong virus (ONNV) | Decreased viral RNA synthesis and protein expression in a dose-dependent manner. | EC50 = 29.2 μM | - | - | CRL-2522 | (Varghese, Thaa et al., 2016)53 |
| Enterovirus 71 (EV71) | Inhibiting EV71 replication (via reduction of viral RNA and protein synthesis as well as inhibiting MEK/ERK pathway), and suppressing virus-induced autophagy (by activating AKT protein and inhibiting JNK and PI3KIII phosphorylation). | IC50 (strain H) = 8.55 μM | 73.10 μM | 8.55 | Vero E6 | (Wang et al., 2017)35 |
| IC50 (strain SHZH98) = 10.25 μM | 73.10 μM | 7.13 | Vero E6 | |||
| IC50 (strain JS-52) = 7.43 μM | 73.10 μM | 9.84 | Vero E6 | |||
| IC50 (strain BrCr) = 7.43 μM | 73.10 μM | 9.84 | Vero E6 | |||
| EV71 | Inhibition of activation of MEK/ERK signaling pathway and suppression of EV71-induced autophagy by activation of AKT and inhibition of phosphorylation of JNK and PI3KIII proteins. | IC50 (strain S) = 21.2 μM | 146.9 μM | 6.93 | Vero E6 | (Wang et al., 2018)54 |
| IC50 (strain JS-52) = 14.0 μM | 147.0 μM | 10.5 | Vero E6 | |||
| IC50 (strain SHZH98) = 28.2 μM | 147.2 μM | 5.22 | Vero E6 | |||
| IC50 (strain BrCr) = 9.45 μM | 147.4 μM | 15.6 | Vero E6 | |||
| Hepatitis C Virus (HCV) | Inhibiting HCV binding and entry/fusion steps without inactivating free virus particles or affecting expression of host cell entry factors and postentry viral replication | EC50 = 7.87 μM | 82.75 μM | 10.51 | Huh-7.5 | (Hung et al., 2019)36 |
| Human cytomegalovirus (HCMV); Different strains | Inhibiting transactivating functions of the viral transcription factor immediate-early 2 (IE2), thus impairing efficient E gene expression and the progression of the viral replication cycle. | EC50 (strain AD169) = 2.65 μM | 390 μM | 147 | HFF | (Luganini et al., 2019)37 |
| EC50 (strain TB40-UL32-EGFP) = 2.70 μM | 390 μM | 144 | HFF | |||
| EC50 (strain VR1814) = 4.00 μM | 390 μM | 98 | HFF | |||
| EC50 (strain 388438U) = 1.30 μM | 390 μM | 300 | HFF | |||
| Murine cytomegalovirus (MCMV) | Inhibiting the activity of the MCMV transcription factor IE3. | EC50 = 1.95 μM | 192 μM | 98 | NIH 3T3 | (Luganini et al., 2019)37 |
| Influenza A H3N2 (strain A/Hong Kong/4801/2014) | Upregulating the MAPK/ERK pathway and hijacking this pathway for nucleolar export of the viral ribonucleoprotein. | IC50 = 17 μM | 107 μM | 6 | A549 | (Botwina et al., 2020)38 |
| IC50 = 52 μM | 1053 μM | 20 | MDCK | |||
| IC50 = 4 μM | 521 μM | 123 | LET1 | |||
| IC50 = 16 μM | - | - | HAE | |||
| HIV-1 (Different HIV-1 pseudotyped viruses) | Disruption of HIV-1 envelope glycoprotein function and inhibition of virus-mediated cell–cell fusion (inhibiting the fusion process of viral entry into host cells). | IC50 (strain IIIB) = 6.356 (μg/mL) | 107 (μg/mL) | - | - | (Shao, Zeng, Tian, Liu, Fu, 2020)55 |
| IC50 (strain NL4–3) = 5.574 (μg/mL) | - | - | ||||
| IC50 (strain Bal) = 5.586 (μg/mL) | - | - | ||||
| IC50 (strain JRFL) = 10.275 (μg/mL) | - | - | ||||
| IC50 (strain JRCSF) = 7.559 (μg/mL) | - | - | ||||
| IC50 (strain AD8) = 7.532 (μg/mL) | - | - | ||||
| SARS-CoV-2 | - | IC50 = 10.58 μM | >400 μM | >37.84 | Vero E6 | (Pizzorno et al., 2020)43 |
| SARS-CoV-2 | Inhibition of viral replication by disrupting the late viral infection cycle and by targeting MAPK pathways (ERK, JNK, and p38 MAPK). | EC50 = 9.1 μM | 149.2 μM | 16.4 | Vero E6 | (Varghese et al., 2021)44 |
| Dengue Virus (DENV) | Two distinct mechanisms of action include direct virucidal activity, as well as inhibiting infectious virus production through an effect on adenosine-monophosphate activated kinase (AMPK) activation and lipid metabolism. | IC50 = 42.87 μM | - | - | BHK-21 | (Ratanakomol, Roytrakul, Wikan, Smith, 2021)39 |
| EC50 = 3.66 μM | 115 μM | 31.42 | BHK-21 | |||
| - | 79.54 μM | - | A549 | |||
| - | 8.24 μM | - | HEK293T/17 | |||
| - | 70.98 μM | - | Huh-7 | |||
| - | 244.1 μM | - | HepG2 | |||
| Zika virus (ZIKV) | - | IC50 = 11.42 μM | - | - | BHK-21 | (Ratanakomol et al., 2021)39 |
| CHIKV | - | IC50 = 14.21 μM | - | - | BHK-21 | (Ratanakomol et al., 2021)39 |
| Cyprinid herpesvirus 2 (CyHV-2) | Inhibiting the viral gene transcription and suppressing the viral replication in a dose-dependent manner | EC50 = 9.74 μg/mL | >25 μg/mL | >2.57 | RyuF-2 | (Su, Tang, Wang, Lu, 2021)40 |
| Herpes simplex virus 1 (HSV-1) | Inhibition of transcription and translation of genes related to HSV-1 activity (gD, ICP-4, ICP-5, and ICP-8) and suppression of phosphorylation of MAPK proteins (JNK and p38). | IC50 = 45.6 μM | 405.11 μM | 8.9 | HEK293T | (Cui, Zhang, Hu, Yang, 2022)56 |
| EV71 | Preventing the viral replication stage by regulating the Keap1- Nuclear factor erythroid 2-related factor 2 (Nrf2) axis, resulting in the abolishing of virus replication and inflammation. | IC50 = 2.79 μM | >100 μM | U251 | (Cui et al., 2022)57 | |
| IC50 = 4.03 μM | >100 μM | SK-N-MC | ||||
| IC50 = 6.83 μM | >100 μM | A549 | ||||
| DENV (different strains) | Suppression of the formation of intracellular and extracellular infectious viral particles (without affecting the early events of the viral replication cycle or viral protein expression), as well as inhibiting the activation of ERK1/2 and p38 MAPK | IC50 (strain Hawaii) = 9.1 μM | >200 μM | >21.9 | Vero E6 | (Giannone et al., 2023)58 |
| IC50 (strain NGC) = 2.4 μM | >200 μM | >83.3 | Vero E6 | |||
| IC50 (strain H87) = 11.6 μM | >200 μM | >17.3 | Vero E6 | |||
| IC50 (strain 8124) = 6.2 μM | >200 μM | >32.3 | Vero E6 | |||
| IC50 (strain NGC) = 2.7 μM | 89.9 μM | 33.3 | A549 | |||
| IC50 (strain NGC) = 3.5 μM | >200 μM | >57.1 | HepG2 | |||
| ZIKV (different strains) | Inhibiting the activation of ERK1/2 and p38 cell signaling pathways caused by ZIKV and reducing p38 MAPK phosphorylation | IC50 (strain INEVH116141) = 5.7 μM | >200 μM | >35.1 | Vero E6 | (Giannone et al., 2023)58 |
| IC50 (strain PRVABC59) = 0.7 μM | >200 μM | >285.7 | Vero E6 | |||
| IC50 (strain DAK-AR-41524) = 3.8 μM | >200 μM | >52.6 | Vero E6 | |||
| IC50 (strain INEVH116141) = 5.6 μM | 89.9 μM | 16.1 | A549 | |||
| IC50 (strain INEVH116141) = 5.6 μM | >200 μM | >35.7 | HepG2 |
a
The SI is a ratio that measures the window between cytotoxicity and antiviral activity by dividing the given CC50 value by the EC50 value (EC50/CC50).