Roorkee (The Hawk): Indian Institute of Technology Roorkee (IIT Roorkee) Researchers have identified anti-viral molecules that can be used effectively to treat COVID-19 infections. The researchers identified three such antiviral molecules through drug repurposing, computational and antiviral experimental studies.
The COVID-19 pandemic spurred both computational and experimental studies all over the world to understand the structure and nature of SARS-COV-2 viral proteins and develop vaccines and cures for it. One important branch of study is structure-function studies to unravel the atomic structures of the virus and its proteins that constitute the virus.
These studies have resulted in the availability of a ‘Protein Data Bank,’ a repository of the structures of proteins and viruses. This PDB databank is used by researchers globally for drug discovery. The IIT Roorkee team is executing protein structure-based drug-repurposing research on SARS-CoV2 molecules for clinical evaluation and eventual use as antiviral therapeutics.
The Research Team was led by Prof. Shailly Tomar, Department of Biosciences and Bioengineering, IIT Roorkee. The Research Paper was co-authored by Ruchi Rani, Siwen Long, Akshay Pareek, Preeti Dhaka, Ankur Singh, Pravindra Kumar, Gerald McInerney, and Prof. Tomar and published in the reputed, peer-reviewed journal Virology (https://doi.org/10.1016/j.virol.2022.08.008 ).
Speaking on the importance of such research, Prof. KK Pant, Director, IIT Roorkee, said, “Such research into SARS-COV-2 virus is critical not only to deal with COVID-19 pandemic but also prepare for any new variants and future pandemics as well. This research can provide valuable inputs to the scientific community to understand such viruses and develop vaccines.”
The IIT Roorkee team used the Protein Data Bank to target and identify drug molecules for the COVID-19 virus. They focused on discovering molecules that acted on a specific part of the viral proteins called the nucleotide-binding pockets (NBPs). As the name suggests, the NBP binds to the nucleotides – the building blocks of RNA and DNA – and help in the replication of the virus. NBP-targeting drugs are known and used for viral diseases such as HIV, hepatitis B, hepatitis C, and herpes, among others.
Presenting the goal of their research, lead researcher Prof. Shailly Tomar, Department of Biosciences and Bioengineering, IIT Roorkee. said, “Given the success of NBP-targeting antivirals in other diseases, we attempted to repurpose pharmacologically-active compounds that bind to the NBPs of six SARS-CoV-2 proteins.” The team identified the six NBPs using the atomic structures available in the Protein Data Bank. The team used a novel approach of multi-targeting various virus-specific proteins using one drug, instead of targeting only one virus-specific protein. This novel multi-targeting approach is expected to be therapeutically highly effective and is less likely to result in resistant variant strains.
Additionally, we used the drug repurposing strategy for the discovery of new anti-SARS-CoV2 molecules from already approved or existing drugs. Without tedious, time-consuming, and expensive drug development studies, molecular therapies based on drug repurposing are ready for clinical trials. IIT Roorkee team using a drug repurposing approach discovered INCB28060, which is a cancer drug; Darglitazone, an anti-diabetic molecule; and Columbianadin, a natural phytochemical with anti-inflammatory and anti-cancer effects - against the Covid-19 virus.
Elaborating further, Prof. Pravindra Kumar, Head, Department of Biosciences and Bioengineering, IIT Roorkee, said, “We characterized the selected molecules based on the binding abilities of these molecules to target protein tested using experimental methods such as isothermal titration calorimetry, their Absorption, Distribution, Metabolism, and Excretion (ADME) properties by simulation studies, and subsequent cell-based antiviral assays. The study was supported by the Intensification of Research in High Priority Areas (IRHPA) program of the Science and Engineering Research Board (SERB), Department of Science & Technology (DST), Government of India.” “The antivirals that target multiple proteins that we have identified will direct the development of antiviral therapy against SARS-CoV-2 and its emerging variants,” added Prof. Pravindra Kumar.