IIT Mandi discover phytochemicals in Himalayan plant that inhibit COVID-19 virus

Researchers show that phytochemical-rich petals of Rhododendron arboreum found in the Himalayan region, locally called “Buransh” show antiviral activity and fight against the virus

Researchers from the Indian Institute of Technology (IIT) Mandi and The International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, have identified phytochemicals in the petals of a Himalayan plant that could potentially be used to treat COVID-19 infections, IIT Mandi said in a statement.

It said that the findings of the research team have been recently published in the journal Biomolecular Structure and Dynamics.

Speaking in this regard, Dr Shyam Kumar Masakapalli, Associate Professor, BioX Centre, School of Basic Science, IIT Mandi, said, “Among the different types of therapeutic agents being studied, phytochemicals – chemicals derived from plants – are considered particularly promising because of their synergistic activity and natural source with fewer toxicity issues. We are hunting for promising molecules from the Himalayan flora using multi-disciplinary approaches.”

The petals of the Himalayan Buransh plant, scientifically called Rhododendron arboreum, are consumed in various forms by the local population for its varied health benefits. The scientists from IIT Mandi and ICGEB set out to scientifically test the extracts containing various phytochemicals in it, with particular focus on antiviral activity. The researchers extracted the phytochemicals from the Buransh petals and performed biochemical assays and computational simulation studies to understand their antiviral properties, added the statement.

Dr Ranjan Nanda, Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, said, “We have profiled and investigated the phytochemicals of Rhododendron arboreum petals sourced from Himalayan flora and have found it to be a promising candidate against the COVID virus.”

The statement notified that hot water extracts from these petals were found to be rich in quinic acid and its derivatives. Molecular dynamics studies showed that these phytochemicals have two kinds of effects against the virus.. They bound to the main protease – an enzyme that plays an important role in viral replication – and to the Human Angiotensin-Converting Enzyme-2 (ACE2) that mediates viral entry into the host cells.

The researchers also showed through experimental assays that non-toxic doses of the petal extracts can inhibit COVID infection in Vero E6 cells (cells derived from kidney of an African green monkey that are commonly used to study infectivity of virus and bacteria), without any adverse effects on the cells themselves, it further mentioned.

Dr Sujatha Sunil, Vector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, said, “A combination of the phytochemical profiling, computer simulations and in-vitro antiviral assays showed that the extracts from the Buransh petals inhibited the replication of the COVID-19 virus in a dose-dependent manner.”

The findings support the urgent need for further scientific studies aimed at finding specific bioactive drug candidates from R arboreum, in vivo and clinical trials against COVID-19. The research team also plans to carry out additional studies to understand the precise mechanism of inhibition of COVID-19 replication by specific phytochemicals from Buransh petals, the statement concluded.

 

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The impact of zinc deficiency on our immunity

As doctors, scientists and researchers globally are still studying the novel Coronavirus and discovering how the infection works and new ways to treat it, there is an avalanche of information that might be conflicting sometimes. However, doctors world over have to come to the consensus that building a robust immune system will give you a better chance of combating the virus should you contract it. Zinc is one such micronutrient that helps in building immunity and recent studies show that zinc inhibits coronavirus by blocking a key enzyme. Scientific evidence documented in the past few decades shows that consumption of zinc plays a significant role against viral infections including human respiratory infections because of its immuno-nutrient properties. According to a study by the Harvard T.H. Chan School of Public Health- ‘Inadequate zinc intake in India: past, present and future’ inadequate zinc intake has been rising in India for decades, causing tens of millions of people to become newly deficient in it. Zinc deficiency has caused a malnutrition problem worldwide. The study states that the highest rate of inadequate zinc intake was concentrated mainly in the southern and northeastern states of India with rice-dominated diets: Kerala, Tamil Nadu, Andhra Pradesh, Manipur and Meghalaya. Thus, zinc intake for Indians is of paramount importance.

Coronaviruses is the old common cold virus which causes 30-40% of common colds discovered in the Common Cold Unit in 1964 form UK .Zinc has been studied for more than four decades in common cold therapies . The odds of getting a cold with people taking zinc preventatively is one third less . Essentially Zinc’s properties help in reducing the severity and duration of the cold. It is an essential mineral that our body cannot make by itself, hence we need to make sure our diet is zinc-rich along with other nutrients.

Zinc deficiency is one of the most common nutritional deficiencies in the world, yet it is essential for healthy immune function. Zinc is needed for immune cell development and communication and plays an important role in inflammatory response. Zinc supplementation may prove beneficial against coronavirus infection by providing an additional immunity defense. This given point in time, keeping your immunity system strong and making healthy lifestyle choices is the need of the hour.

Also, assessment of nutritional status of COVID19 patients before administration of general treatment is important as immune response is weakened due to inadequate nutrition. We all need to build strong immnunity in corona and covid times like a safety net or “kavach” around us.

Fortifying your immunity system against colds and flu’s is essential now more than ever. A balanced diet and attention to macro and micronutrients is the basis of building a vigorous immune system. Your meal needs to have the right amount of vitamins, minerals and carbohydrates. Zinc also should be consumed judiciously because an overdose of zinc can cause indigestion, headaches and nausea. Zinc not only has immunity-boosting properties but also makes sure your metabolism is strong. Its important to have the right amount of zinc in your body. 

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Chemists develop promising molecular tool to target cell immortality's underlying gears

One of the hallmarks of cancer is cell immortality. A Northwestern University organic chemist and his team now have developed a promising molecular tool that targets and inhibits one of cell immortality's underlying gears: the enzyme telomerase.

This enzyme is found overexpressed in approximately 90% of human cancer cells and has become an important subject of study for cancer researchers. Normal cells have the gene for telomerase, but it typically is not expressed.

"Telomerase is the primary enzyme that allows cancer cells to live forever," said Karl A. Scheidt, who led the research. "We want to short-circuit this immortality. Now we have designed a first-of-its-kind small molecule that irreversibly binds to telomerase, shutting down its activity. This mechanism offers a new pathway for treating cancer and understanding cellular aging."

Scheidt is a professor of chemistry in the Weinberg College of Arts and Sciences and a professor of pharmacology at Northwestern University Feinberg School of Medicine.

The big idea for the small molecule design came from nature. A decade ago, Scheidt was intrigued by the biological activity of chrolactomycin, which is produced by bacteria and has been shown to inhibit telomerase.

Scheidt and his team used chrolactomycin as a starting point in the design of their small molecules. They produced more than 200 compounds over the years, and the compound they call NU-1 was the most effective of those tested. Its synthesis is very efficient, taking fewer than five steps.

    NU-1 inhibits telomerase unlike anything that came before it. It does this by forming a covalent bond. Another advantage of NU-1 is that its molecular structure should enable scientists to add cargo, such as a therapeutic." Karl A. Scheidt, professor of pharmacology at Northwestern University Feinberg School of Medicine.

The study was published last week by the journal ACS Chemical Biology.

All human cells have telomeres, short DNA sequences that cap the ends of each strand of DNA. Their job is to protect our chromosomes and DNA. When a cell divides, the telomeres get shorter until they can no longer do their job. Natural cell death follows.

In contrast, cancer cells, with their heightened telomerase activity, become immortal by reversing the normal telomere shortening process. The enzyme telomerase copies telomeres over and over again, lengthening the telomeres. The result is unlimited cell division and immortality. The famous HeLa cells, isolated from the cervical cancer tissue of Henrietta Lacks in the 1950s, are still dividing.

Telomerase has been a target for cancer therapeutics research for decades. In 2009, three scientists received the Nobel Prize in Physiology or Medicine for their earlier research into telomeres and telomerase.



After developing their new compounds, Scheidt and his team initiated collaborations with Professor Stephen Kron at the University of Chicago and Scott Cohen at the Children's Medical Research Institute in Sydney to investigate the extra-telomeric role of telomerase inhibition.

The studies focused on how the new compounds interact with telomerase on a molecular level and how telomerase inhibition sensitizes cells to chemotherapies and irradiation. From this work, NU-1 rose to the top.

"By publishing this study, we are test driving this exquisite tool to see what it can do and to learn more about telomerase," Scheidt said. "We also are continuing to make it better."

The research was done in human cells. The next steps, Scheidt said, are to make more potent compounds and investigate them in animal models.

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