The Biopharmaceutical Complex is currently preparing bird flu mRNA injections developed by Moderna, CEPI-funded H5N1 replicon (self-amplifying) shots, and Arcturus Therapeutics replicon ‘pandemic’ bird flu injections funded by BARDA and the Gates Foundation. Thus, it is of high priority to identify promising compounds with anti-avian influenza activity that don’t involve injection of modified genetic material.
Methods: 33 plants and 4 natural compounds were identified and documented. Molecular docking was performed against the target viral protein neuraminidase (NA), with some plant based natural compounds and compared their results with standard drugs Oseltamivir and Zanamivir to obtain novel drug targets for influenza.
Results: It was seen that most extracts exhibit their action by interacting with viral hemagglutinin or neuraminidase and inhibit viral entry or release from the host cell. Some plants also interacted with the viral RNA replication or by reducing proinflammatory cytokines. Ethanol was mostly used for extraction. Among all the plants Theobroma cacao, Capparis Sinaica Veil, Androgarphis paniculate, Thallasodendron cillatum, Sinularia candidula, Larcifomes officinalis, Lenzites betulina, Datronia molis, Trametes gibbose exhibited their activity with least concentration (below 10 μg/ ml). The docking results showed that some natural compounds (5,7- dimethoxyflavone, Aloe emodin, Anthocyanins, Quercetin, Hemanthamine, Lyocrine, Terpenoid EA showed satisfactory binding affinity and binding specificity with viral neuraminidase compared to the synthetic drugs.
Table 2 shows the list of medicinal plants with their bioactive extract/constituents reported to have in-vivo (in a living organism) anti-influenza activity:
Table 3 shows the list of medicinal plants with their bioactive extract/constituents reported to have In-vitro (in a test tube) anti-influenza activity:
Molecular docking revealed that some natural compounds could have the potential to bind to the NA protein even stronger than the current synthetic drugs:
From molecular docking results it can be concluded that many natural compounds obtained from the table had higher affinity in the target protein. 5,7- dimethoxyflavone (−7.6), Aloe emodin (−7.7), Anthocyanins (−7.5), Catechin hydrate (−8.2), Epicatechin gallate (−9.3), Lyocrine (−7.1) had significant higher binding affinities then the standard drugs Zanamivir (−7.1) and Oseltamivir (−5.7) with NA. This suggests that our natural compounds could have the potential to bind to the NA protein even stronger than the current synthetic drugs. As the NA is an essential part of viral release from the cell, the compounds hold the possibility to block this and thus inhibit influenza virus infections.
The authors suggest, “compounds such as aloeemodin, quercetin, curcumin, and epicatechin gallate all possess potential to be drug development targets due to their high binding affinity and binding region specificity.”
Instead of mainly funding experimental synthetic products, our public health agencies should begin to investigate natural compounds as potential prevention methods or treatments for avian influenza. Meaningful investigation of inexpensive and non-patentable products will likely require a clean sweep of corruption from the agencies.
Nicolas Hulscher, MPH
Epidemiologist and Foundation Administrator, McCullough Foundation