The upsurge in the current cases of COVID-19 poses a major threat to human health. The emergence of new infectious diseases and the increase in the frequency of drug-resistant viruses demand effective and novel therapeutic agents.
Now researchers, using a bioinformatics approach to investigate the possible inhibitory potential of some constituents of bitter leaf (Vernonia amygdalina) towards coronavirus-2 major protease, say that bitter leaf could be a better drug candidate against COVID-19.
The researchers who examined the profiles of the compounds in bitter leaf said some chemical substances in it showed good binding affinity to the binding pocket of PDB ID 6LU7 (crystal structure of SARS-COV2) even as it exhibited the highest binding affinity when compared to many antiviral agents (remdesivir, hydroxy-vernolide, vernodalin, vernodalol, and vernolide).
Its pharmacodynamics and pharmacokinetics results suggested that all the tested chemicals derived from the bitter leaf have significant drug-likeness properties and they could be absorbed through the human intestine. Furthermore, all the tested chemicals from its leaf show that it is not toxic to the liver and also exhibited none or relatively low toxic effects in human.
Taken together, they declared that the results of this study indicated that all the tested chemicals from bitter leaf are potential putative inhibitors of SARS-COV2 major protease with none or low toxicity effects.
According to them, “the tested phytochemicals exhibited significant binding affinity to the binding pocket of SARS-COV2 major protease suggesting them as potential molecules that could mitigate/inhibit SARS-COV2. The binding of these phytochemicals to SARS-COV2 could inhibit or interfere with the pathogenesis of COVID-19 thereby preventing its cellular entry and proliferation.”
However, they said in the 2021 edition of Computational Toxicology that further experimental and clinical studies are needed to further explore their activities and validate their efficacies against COVID-19.
The study, which investigated the inhibitory potentials of some naturally occurring chemicals present in bitter leaf against COVID-19 involved Johnson Olaleye Oladele at the Kings University, Ode-Omu, Osun State in collaboration with Oyedotun Moses Oyeleke, Oluwaseun Titilope Oladele and Adenike Temidayo Oladiji.
Until now, bitter leaf was widely consumed as a vegetable for its rich array of nutritional components and phytochemicals which are responsible for the various health and medicinal benefits attributed to it.
Due to its numerous medicinal benefits, the leaf of bitter leaf has found wide application in various aspects of traditional medicine including skin problems like rashes, eczema, and ringworm and treatment of many ailments from malaria, typhoid, diabetes, diarrhoea, tuberculosis, gallstones and kidney disease, to the prevention of cancer and lowering of hypertension.
Also, researchers had previously reported that Vernodalin and vernolide, chemical substances in bitter leaf, which showed good binding affinity to the binding pocket of PDB ID 6LU7 have the potential to be used as lead compounds in the development of a therapeutic natural product for the treatment of cancers in the lungs, breast or liver.
Many research groups around the world listed medicinal plants as having potential for the treatment of COVID-19 in the March edition of Frontier of Pharmacology, including their limitations. The topmost of these listed medicinal plants for probable use is Nigella sativa (black cumin), bitter leaf, neem plant, Eurycoma longifolia. These are plants with reported antiviral, anti-inflammatory, and immune-boosting effects.
Only the neem reported positive antiviral evidence specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on preliminary data while all four medicinal plants demonstrated differential anti-inflammatory or immunomodulatory effects.
While the definitive roles of these medicinal plants in cytokine storms and post-infection complications remain to be further investigated, they suggested that quality control and standardisation of medicinal plant-based products also need to be emphasized. However, given the unprecedented challenges faced, ethnopharmacological research should be given a fair amount of consideration for contribution to this pandemic.
Traditionally, N. sativa is used for a diverse range of indications including in respiratory diseases such as asthma. The benefits of N. sativa supplementation in improving asthmatic symptoms have also been reported in a clinical trial. As for safety, long-term consumption (up to three months) of N. sativa seeds at 3 g/day in humans reported no significant adverse effects on both liver and kidney functions.
Water extracts of bitter leaf showed positive effects in enhancing immune response by increasing the levels of white blood cells and CD4+. With the capability to increase the CD4+ cell counts, this extract was reported to be adjuvant to antiretroviral therapy in HIV positive patients. Besides, the aqueous extract also demonstrated potential immune augmenting effects as an adjuvant to the Hepatitis B vaccine.
The extracts of neem leaves, under laboratory conditions, have direct antiviral effects against various viruses including dengue and Hepatitis C Virus. As for immunomodulatory effects, both neem seeds and leaves reported positive effects in enhancing an immune response in animals.
However, the main issue with exploring neem’s potential for COVID-19 is its safety profile. Although neem leaves have been used traditionally for a long time, well-documented safety records are still insufficient.
Several animal toxicity studies have reported variable adverse effects including irregular heartbeats (arrhythmia), low blood sugar level (hypoglycaemia), and blood pressure reduction at high doses of neem leaf extracts. Human cases of kidney injury have also been reported on neem seed oil consumption. In pregnant women, neem seed extracts should be avoided as animal studies have shown they can induce miscarriage.
