AI helps IICT scientists spot promising drugs for Monkeypox, LSDV

Scientists at the CSIR-Indian Institute of Chemical Technology (IICT) have reported a significant advance in computational drug discovery, using artificial intelligence (AI) to identify potential therapies for poxvirus infections, including zoonotic infections like Lumpy Skin Disease Virus (LSDV) and monkeypox.

Lead scientist Ramars Amanchy’s lab research specifically focused on LSDV, which severely affects cattle, along with monkeypox (Mpox), which continues to pose a public health concern. These viruses belong to the Poxviridae family, which also includes the deadly variola virus responsible for smallpox, underscoring the importance of preparedness against potential outbreaks.

To address the lack of validated antiviral targets, the IICT team developed an AI-enabled structural bioinformatics pipeline. This integrated approach combines sequence conservation analysis, phylogenetic mapping, advanced protein structure prediction tools such as ‘AlphaFold2’ and ‘ESMFold’, active-site mapping, molecular docking, molecular dynamics simulations and cheminformatics profiling, said Mr. Amanchy.

Using this framework, the researchers identified two conserved kinases as promising drug targets. These are enzymes used by viruses to evade the immune systems. The analysis primarily focused on LSTK and researchers identified ‘lapatinib’ drug as a potential competitive inhibitor.

The compound demonstrated stable binding and favourable interaction energies during simulations. Further analysis showed that these kinase inhibitors share physicochemical properties with existing veterinary antivirals, suggesting potential for real-world applications.

Importantly, the study highlights the value of drug repurposing ”using existing approved medicines for new therapeutic purposes” as a faster and more cost-effective alternative to traditional drug development, said the senior scientist 

A combinatorial analog library to support future experimental validation and optimisation was also developed by the research team also including Vyshnavi Racha, Anmol Sinha, Apara Chengalvala, Juli Gupta, Saikumar Nalla, Pranav Bhamidipati and Poornachandra Yedla.

Mr. Amanchy noted that viruses like LSDV and monkeypox not only threaten health but also disrupt economies and livelihoods. The AI-driven approach demonstrates India’s potential to develop rapid, affordable solutions for global health challenges.

While the findings are promising, the researchers emphasised that laboratory validation ”including biochemical assays and antiviral studies” will be essential to confirm the therapeutic potential of these compounds. The study, ‘AI-Enabled Structural Bioinformatics Identifies Repositioned Kinase Inhibitor Against Poxviridae Kinases’, has been accepted for publication in the journal Computers in Biology and Medicine.