Recent studies at ICGEB New Delhi in the battle against Covid19 are leading to further exploration of experimental validation and therapeutic possibilities and have been submitted for funding to BIRAC under a call to fight the pandemic.
Neel Sarovar Bhavesh, Transcriptional Regulation, and Dinesh Gupta, Translational Bioinformatics are driving specific leads in the battle against Covid19. Anmol Chandele, Emory Vaccine Program, is at an advanced stage of obtaining regulatory clearances in her team’s repurposing drug trial. There is extensive interaction between ICGEB labs in New Delhi and Trieste in screening for novel antiviral compounds, and assessing them in a variety of different assays.
One of these is exploring the potential repurposing of the approved drug Valproic Acid against SARS-CoV2. The Bhavesh lab has carried out virtual screening of a library containing 1.2 million small molecules, and have found that Valproic Acid Coenzyme-A, a metabolite from the prodrug valproic acid, binds stably to the SARS-CoV2 RNA-dependent RNA polymerase (RdRp).
We had suggested repurposing of Valproic acid Co-A as an inhibitor of SARSCoV2 RdRp using computational tools. Although it had shown binding with the SARSCoV2 RdRp in vitro assay. However, Valproic acid did not show antiviral activity in the plaque assay done in the group of Dr. Alessandro Marcello at ICGEB Trieste, Italy. This data is now being combined and will be put together on the Preprint platform soon. So this can not be taken further at this juncture.
Dinesh Gupta’s Group is using a bioinformatics approach to perform comparative analyses of SARS-CoV2 genomes from different geographical locations with genomes of other coronaviruses to monitor SARS-CoV2 transmission and its sequence variations, with a particular emphasis on looking for variants that may have different degrees of pathogenesis. Analysis so far has revealed a unique mutation in the Indian SARS-CoV2 strain. The Group has also shown that the potently anti-viral human microRNA hsa-miR-27b has a target only in the human strain of the virus, and intends to continue further computational analyses involving more genomes as they become available.
A team at ICGEB New Delhi comprising Pawan Malhotra, Asif Mohmmed and Dinesh Gupta is developing lead molecules for the inhibition of SARS-Cov2 attachment, entry, and infection, exploring known, and new, potentially druggable targets on the virus. In our New Delhi labs we are also attempting to identify human monoclonal antibodies with therapeutic potential by screening patients who have successfully resolved the infection. This is particularly promising, repurposing techniques used successfully in our work on dengue. Anmol Chandele is working towards making human monoclonal antibodies against the SARS-CoV2 strain isolated within India, in collaboration with the Translational Health Science and Technology Institute, THSTI, and the Indian Council of Medical Research, ICMR. Together with Navin Khanna, Translational Health Group, and the Manipal Academy of Higher Education, MAHE, a proposal for the development and evaluation of the SARS COV-2 virus antibody ELISA and Point-of-care test (POCT) has been submitted to the Government of India, Department of Biotechnology funding agency, BIRAC. This team will design, clone, express and purify a multi-epitope protein (MEP) of the SARS COV-2 virus and evaluate its performance using patient sera. This test will be able to score SARS COV-2 seroconversion in a low resource setting.
A team comprising Arockiasamy Arulandu, Sujatha Sunil and Alessandro Marcello, together with Ruhvenile Biomedical OPC Pvt. Ltd., India, propose to develop novel therapeutics against COVID-19, through the design and synthesis of small molecular inhibitors specifically targeting SARS-CoV-2 viral replication. Sujatha Sunil, Vector Borne Diseases Group Leader, in collaboration with the Siddha Central Research Institute, Chennai, has proposed exploring the development of novel herbal formulations against SARS-CoV-2, using traditional medicinal knowledge and modern scientific methods.
In South Africa, the ICGEB laboratories in Cape Town are offering their facilities and services to directly assist in the country’s diagnostic efforts, thereby allowing more samples to be tested each day. Furthermore they are acting as a hub for sharing information about ICGEB’s activities across the African continent, in close collaboration with the Government of South Africa, Department of Science and Innovation.
On 1 April 2020, the publication by the Regione FVG Laboratory Group on COVID19 on the “Isolation and full-length genome characterization of SARS-CoV-2 from COVID-19 cases in Northern Italy” was released in the American Society for Microbiology, Journal of Virology. The ICGEB is also producing reagents for the development of serological diagnosis and provides free, latest information on how to diagnose infection and information on primers, PCR protocols and RNA extraction procedures, which can be developed ‘in house’ and do not require bought-in kits. The contact for further information is available at: [email protected]
The ICGEB is offering positive control RNA, and information for isolating and working with the virus, and for sequencing for subsequent surveillance purposes. All of this is backed up by direct technical assistance with on-line video tutorials on the isolation and detection of Sars-CoV-2 RNA. Protocols and expertise in the production of Interferon alpha, which has been reported to have some beneficial effects in the treatment of Covd19 infections, is also being made freely available on the website, together with links to additional reading, and the possibility for in-house training in its production.
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27 March 2020
Press Release
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Press Contact: Suzanne Kerbavcic
[email protected]
Human topoisomerase I bound to double-stranded DNA. Topoisomerases are enzymes that regulate the winding of DNA helix. Cartoon model with semi-transparent surface.
