Ranchi, JHARKHAND / Riyadh, SAUDI ARABIA :

A collaborative study between scientists in India, Saudi Arabia and South Korea aimed at discovering potential drugs to SARS-CoV-2 infection in humans has led to new findings that could pave way for clinical trials to cure the Coronavirus disease.

The recent study is titled ‘Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 Mpro enzyme through in silico approach. ‘ It has been co-authored by Dr. Arun Bahadur Gurung (North-Eastern Hill University, Shillong), Joongku Lee (Chungnam National University, South Korea) and three others, Dr. M. Ajmal Ali, Dr. Khalid Mashay Al-Anazi along with Dr. Mohammad Abul Farah (King Saud University).

The research has used screening from FDA approved antiviral drugs applying computational approach to embark on a scientific experimentation of vaccine development for the disease.

Dr Mohammad Abul Farah, originally from Ranchi in the Indian state of Jharkhand, spoke with TwoCircles.net about the study that has revealed substances and proteins having high capabilities of being used in treatment of the COVID-19 disease. An alumnus of Aligarh Muslim University, he is currently Professor at Saudi Arabia’s King Saud University and closely associated in the Genetics Laboratory at its College of Science in the Department of Zoology.

Having more than a decade of experience in academics and research in cytogenetics and genotoxicity, he is also working with Proteonik Inc, a South Korea based biotechnology research organization. 

He opines that “the discovery of novel drug molecules is crucial and is need of the time” as mortality rate due to Coronavirus is rising exponentially and the speed for finding a vaccine must be accelerated with more variety in clinical lab experiments. He explained that at present there are no approved antiviral drugs or vaccines for the treatment of human CoV infection therefore the scientists in this study were compelled to use computational methods to address the problem and build on effective therapeutics against the current pandemic.

Dr Farah informed that the researchers have proposed “potential lead molecules which can be explored as drug candidates for the treatment of the COVID-19 disease.” He further detailed the findings of the study for TwoCircles.net, beginning with the fact that “SARS-CoV-2 Mpro protease enzyme is a well-characterized drug target.” Through the study’s recent structural elucidation based on X-ray crystallography, it has opened an avenue for structure-based drug design. They have also explored “a small library of phytochemicals with previously reported antiviral properties for the identification of small molecular inhibitors against SARS-CoV-2 Mpro enzyme” leading to identification of three lead molecules which exhibit higher binding affinities as compared to the control.

“The findings are novel and exciting as the lead molecules also demonstrated broad-spectrum antiviral activities against SARS-CoV Mpro and MERS-CoV Mpro,” he informed. He also outlined that the scientists screened small drug-like molecules from a dataset of phytochemicals possessing antiviral activities and this was achieved with the help of drug-like filters and toxicity studies. The selected molecules were evaluated for their binding affinity to SARS-CoV-2 Mpro enzyme using molecular docking, from which a total of 38 phytochemicals belonging to the class of flavonoids, alkaloids, essential oils, organic acids, stilbenes and other phytoconstituents were screened. This led to identification of three lead molecules – Bonducellpin D and Caesalmin B and 5,7-dimethoxyflavanone-4′-O-β-d-glucopyranoside – all three having antiviral activities against parainfluenza virus (PI-3) and bovine (cattle) virus. These three lead phytochemicals, he says, “have potential to be developed as effective antiviral drug specifically against SARS CoV-2.”

When asked whether this identification would accelerate the process of vaccine formation or not, Dr Farah pointed that antiviral drug development takes place via classical mechanisms – usually by targeting important virus enzymes such as polymerases, proteases or neuraminidase; however vaccine against a specific virus is developed by injecting the same virus in inactive form or non-pathogenic form to activate the host immune system to produce specific antibodies against the virus. For that, he said “the current findings need further validations through in vitro and in vivo lab experiments for developing into drug candidate molecules.”

Bonducellpin D is a promising drug candidate against coronavirus, suggest the findings. While the three substances were found to be “significantly inhibiting Mpro enzyme that ultimately block the viral replication,” Bonducellpin D was identified as a unique precursor to a vaccine for coronavirus.

Discussing India’s more than 1 lakh mark of current infection rates coupled with a fourth phase of a nationwide lockdown and massive breakdown of economy unfolding with the migrant crisis, Dr Abul Farah highlighted that all the three lead molecules that need further validations through lab experiments can be obtained through a clinical manufacturing company and in case they are not available commercially, they can easily be purified from the source (plant), or could be synthesized in any chemistry lab equipped for organic synthesis.

“Of course, India can afford all these kind of research,” he said, when inquired about the feasibility of obtaining or manufacturing the same molecular binding in research labs in the country. He assured that India has “many high standard virology and clinical trial labs,” and the substances for clinical experiments can be obtained easily.

(The research paper can be accessed here: https://www.sciencedirect.com/science/article/pii/S0024320520305816)

source: http://www.twocircles.net / TwoCircles.net / Home> TCN Positive> Indian News> Lead Story> Pandemic> Science/Health / by TCN News / May 28th, 2020