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Coronavirus: Study finds neem tree-based drugs may help fight COVID

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Can Neem bark extract reduce the severity of SARS-CoV-2 replication, spread and pathogenesis as it does for murine group 2 beta coronavirus?



The current outbreak of the novel coronavirus, Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), has brought the entire world to adead stop. SARS-CoV-2 is an enveloped positive-sense single-stranded RNA virus. It is causing severe acute respiratory distress syndrome (ARDS). COVID-19 has significant health and economic consequences due to its aggressive virulence and potential lethality for older age groups.Whole world is looking for an effective diagnostics and anti-viral therapeutic targets.

Jayasri Das Sarma, Professor, Department of Biological Sciences and her research team from Indian Institute of Science Education and Research Kolkatahave spent considerable time studying the murine coronaviruses focussing on understanding key mechanisms underlying infection, viral spread, host immune responses, and related pathogenesis.She has extensively used the murine group II beta-coronavirus (mouse hepatitis virus; MHV) as her test system, with a focus to understand the molecular mechanisms of infection-initiation mediated by a key protein called the Spike Glycoprotein.Mouse hepatitis virus only infects mice and there is so far no history of human infection.

Dr. Das Sarma and her Integrated Ph.D student Ms. Lucky Sarkar, Int. BS-MS student Mr. Ravi Kiran Putchala and International Ph.D student Abass Alao Safiriyu tested the antiviral properties of Neem (Azadirachticaindica) bark extract (NBE) against MHV infection and immuno-pathogenesis. Their studyshowed that NBE is successfully able to control MHV replication, cell-to cell spread and acute hepatitis (inflammation in the liver), meningitis (inflammation in meninges), encephalitis (inflammation in brain), myelitis (inflammation in spinal cord), and chronic progressive demyelination (loss of myelin sheath and axonal loss) in MHV-induced experimental animal model.These neurological symptoms mimic certain pathology of human neurological disease multiple sclerosis (MS).This work has been accepted in international peer reviewed journal “Frontiers in Cellular Neuroscience” on April 14, 2020. This work has also been selected for the highlights in ‘American Society for Virology (ASV 2020)’ conference proceedings.

MHV Spike protein (virus-host attachment protein) is known to cause cell-to-cell fusion as well as virus-to-host cell fusion. Anti-viral properties of NBE are likely due to its ability to reduce cell-to-cell fusion, thereby decreasing pathogenicity and disease severity.
To look for an effective bioactive compound in NBE, Dr. Das Sarma in collaboration with Dr. Debnath Pal, computational biologist at IISc Bangalore is carrying out the in silico molecular docking studies which can contribute towards the anti-viral activity of NBE. Their virtual high-throughput screening via structural modelling and analysis (including dynamics) of spike protein revealed that limonoids and tetraterpenoids group of compounds of NBE might have the potential to block the binding ability to the host cell as well as virus-to-host cell fusion.

As SARS-CoV-2 is also a beta coronavirus like MHV and their Spike protein shares 37% sequence similarity we are hoping that NBE may also interact with the SARS-CoV-2 spike protein and attenuates its infection-initiation, viral antigen spread, viral replication, and consecutive pathogenesis. Dr. Das Sarma with her team is trying to set up a virus-free cell culture based assay system to test the efficacy of NBE and its compound against SARS-CoV-2 at IISER Kolkata, whereas Dr. Debnath Pal at IISC is trying to do the molecular modelling of SARS-CoV-2 spike protein with NBE to find the active binding partner/compound.

Dr. Ujjwal Neogi, one of the collaborators of Dr. Das Sarma from Karolinska Institute, Sweden kindly agreed to test the efficacy of NBE binding with Swedish SARS-CoV-2 Spike protein in their BSL3 facility as Dr. Das Sarma does not have BSL-3 facility at IISER Kolkata.

Dr. Das Sarma and her team sincerely hope that soon they will come up with the answer to know whether NBE can bind to the SARS-CoV-2 Spike also to exert its ameliorative effect to control SARS-CoV-2 and can reduced the severity of COVID-19.

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