In a recent review in the journal Viruses, researchers look at natural products that can be identified as potential alternative antiviral agents. The reviewers discussed the antiviral activities of several natural products towards DNA and RNA viruses with an analytical approach. The researchers detailed the cellular/viral targets of the active molecules and their impact on the infection and viral replication cycle.
Several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are associated with high morbidity and mortality rates in humans. Most plant-derived compounds, especially small organic compounds named secondary metabolites, are potent therapeutic agents for chronic diseases, degenerative processes, carcinogenesis, and antiviral activity.
Notably, although natural compounds are primarily used as unpurified raw extracts, the isolation of these biomolecules is crucial for predicting their properties related to the pharmacokinetics and pharmacodynamics of a drug molecule (absorption, distribution, metabolism, excretion, and toxicity).
Phytochemicals, such as coumarins, flavonoids, terpenoids, organosulfur compounds, lignans, polyphenols, saponins, proteins, and peptides are reported to influence cellular functions, membrane permeability, and viral replication - significant targets that generally fetch successful antiviral efficacy.
Natural compounds against DNA viruses
Hepatitis B Virus (HBV), Herpes Simplex Virus (HSV-1), and the Human Papilloma Virus (HPV)
HBV is known to infect the liver and cause acute and chronic inflammation in hepatocytes. The reviewers presented nine natural compounds against the Hepatitis B virus (HBV), along with the antiviral targets. These compounds target and Inhibit the viral entry, replication, and maturation of the HBV particles. Some of these also target host cellular factors such as enhance ROS by suppressing the manganese superoxide dismutase (SOD2) expression, inhibit the transcription of HBV X (HBx) gene through a p53-mediated pathway, or activate via g the NF-κB (nuclear factor kappa B) signaling pathway.
Likewise, HSV-1, which causes oral and genital infections and is highly prevalent, presents six natural antiviral compounds. Turmeric, pistachio, aloe vera, conifers, chameleon, and almonds are some of the plants that are sources of the natural antiviral compound against HSV-1.
Polyphenols from natural and herbal extracts are reported as powerful and safe anticancer compounds. HPVs are sexually transmitted viruses, infecting about 80% of the sexually active population; also associated with cervical cancer. The natural product downregulates the expression of oncogenes, prevents viral entry, promotes apoptosis, and inhibits cellular transcriptional factors. The reviewers tabulated the interesting natural sources and the active compounds against the different HPVs.
Against adenoviruses, only two antiviral drugs, ribavirin, and cidofovir, are currently used in anti-adenoviral therapy. Drug resistance has pushed research towards new avenues. Asian countries such as China, India, and Taiwan, use medicinal plants as the primary source of antiviral drugs. The reviewers tabulated over 15 natural antivirals against the adenoviruses.
Natural compounds against RNA viruses
Human Immunodeficiency Virus (HIV), Influenza Viruses, Hepatitis C Virus, Picornaviruses, Norovirus
The reviewers summarized over 50 natural compounds that act against the RNA viruses. The reported action of the antiviral compounds are generally: 1) as critical inhibitors (at viral entry, maturation, replication), 2) to block (ROS)-dependent ERK phosphorylation, 3) as Haemagglutinin inhibitors, 4) suppression of the helicase activity, 5) to target host cellular factors, or 6) reduce genome replication.
Natural Compounds against Emerging and Re-Emerging Viruses
Coronaviruses, Flaviviruses, Togaviruses, Filoviruses
Discussing coronaviruses in the wake of the COVID-19 (coronavirus disease 2019) pandemic, the reviewers summarized the natural compounds that specifically target the viral proteins, the mRNA translation, or exhibit broad-spectrum activity (curcumin).
"The spike glycoprotein represents the therapeutic target of natural compounds such as emodin extracted from Rheum officinalis, ginsenoside-Rb1 extracted from Panax ginseng, secomet-V extracted from African trifolium and tetra-O-galloyl-β-D-glucose extracted from Galla chinensis to SARS-CoV, saikosaponin B2 extracted from Bupleurum chinense to HCoV-229E."
Flaviviruses are enveloped, single-stranded RNA viruses that are transmitted by either mosquitoes or ticks (arthropod-borne). These are important pathogens such as the Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), and West Nile virus (WNV). The Chikungunya virus (CHIKV) is also a mosquito-transmitted alphavirus belonging to the family Togaviridae. The Ebola virus (EBOV) is amongst the most pathogenic viruses; it causes viral hemorrhagic fever outbreaks in Africa, with human case fatality rates of up to 90%. EBOV virus belongs to the Filoviridae family. No vaccine or drug has been approved so far.
Compounds such as Epigallocatechin gallate (from green tea), rutin, quercetin, and ellagic acid, the flavonoids baicalein, fisetin, and quercetagetin, berberine, rocaglate silvestrol (isolated from Aglaia plant), galactomannans, aqueous extracts from Azadirachta indica, eugenol, p-anisaldehyde, etc. are some of the natural antivirals summarized against these epidemic viruses.
The authors conclude, "A large number of natural products have been reported to have potential in vitro and in vivo antiviral activities in pre-clinical studies, and some have been included in clinical trials for drug development. Unlike combinatorial synthetic drugs, these natural active compounds have high biochemical specificity against a wide range of molecular targets while remaining capable of being absorbed and metabolized with low toxic effects. Another serious problem in viral pathogenesis is represented by emerging and re-emerging viruses, which have resulted in many outbreaks, epidemics, and pandemics, including the current emergence of COVID-19 disease due to the worldwide spread of SARS-CoV-2, affecting both social and economic conditions worldwide. Although large numbers of natural compounds have been isolated from medicinal plants, only a few have been marketed as pharmaceutical products. Thus, further characterization of the active compounds will be helpful in the treatment of viral infections and the management of pandemic outbreaks."