New Delhi, Nov. 02 (India Science Wire): Researchers at the Indian Institute of Technology (IIT) Roorkee, have identified antiviral molecules that can help treat COVID-19 infections. The researchers identified three antiviral molecules through drug repurposing, computational and antiviral experimental studies.
The COVID-19 pandemic spurred both computational and experimental studies worldwide 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 the proteins that constitute the virus.
These studies have resulted in a Protein Data Bank (PDB), a repository of the structures of proteins and viruses. This PDB is used by researchers globally for drug discovery. The IIT Roorkee team is executing protein structure-based drug-repurposing research on SARS-CoV2 m,olecules for clinical evaluation and eventual use as antiviral therapeutics.
The research team led by Professor Shailly Tomar, Department of Biosciences and Bioengineering, IIT Roorkee, 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, to facilitate virus replication. NBP-targeting drugs are known and used for viral diseases such as HIV, Hepatitis B, Hepatitis C, and Herpes, among others.
The team identified the six NBPs using the atomic structures available in the Protein Data Bank. The researchers 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.
The research study co-authored by Ruchi Rani, Siwen Long, Akshay Pareek, Preeti Dhaka, Ankur Singh, Pravindra Kumar, and Gerald McInerney, has been published in the journal Virology.
“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”, said Prof. Shailly Tomar.
Drug repurposing strategy is used to discover 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, , 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,” explains Prof. Pravindra Kumar, Head, Department of Biosciences and Bioengineering, IIT Roorkee.
“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.
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 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. (India Science Wire)
ISW/USM/IIT-Roorkee/Covid-19/Eng/02/11/2022
Ankur Singh, Preeti Dhaka, Prof. Pravindra Kumar, Prof. Shailly Tomar & Ruchi Rani (L to R)
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