Study finds a new way to diagnose and treat Monkeypox

A team of researchers of Bengaluru-based Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), an autonomous institution of the Government of India’s Department of Science and Technology (DST), has identified a new way to understand the virology of Monkeypox virus (MPV) and develop diagnostic tools for the infection and find novel paths with therapeutic implications.

Outbreak of Monkeypox disease, also known as Mpox, was recently declared a Public Health Emergency of International Concern (PHEIC) twice within a span of three years. It has raised serious concerns about its spread across the globe, as the modes of transmission and symptoms are not well understood. A comprehensive understanding of virology, alongside the rapid development of effective diagnostic and therapeutic strategies, is of paramount importance.

MPV is a double-stranded DNA (dsDNA) virus. The detection of the extracellular viral protein gene through polymerase chain reaction (PCR) is a widely established technique for identifying MPV in clinical specimens. Common detection approaches, including PCR, rely on the amplification of double-stranded DNA (dsDNA). They employ fluorescent probes for quantifying amplification.

While these probes are sensitive to dsDNA concentration, they lack the ability to differentiate between specific and non-specific amplification products. In contrast, specific sequences in DNA can fold into unique structures that deviate from the classical double helix, known as noncanonical nucleic acid conformations. Leveraging the potential of these unusual DNA structures as targets for small-molecule fluorescent probes, may open new avenues for the development of highly reliable diagnostic assays.

G-quadruplex (GQ) is one such unusual non canonical conformation observed in guanine (G)-rich nucleic acid sequences where four guanines interact through hydrogen bonding forming a planar G-tetrad plane, and the stacking of multiple G-tetrads results in GQ formation.

Scientists from JNCASR,  have identified and characterised highly conserved GQ forming DNA sequences—a set of four, within the MPV genome, and have detected a specific GQ sequence using a tailored fluorescent small-molecule probe. This enables precise detection of the virus. The identification, characterization and targeting of unusual nucleic acid structures such as GQs also have therapeutic implications.

The study was conducted by Sumon Pratihar, Ramjayakumar Venkatesh, Mohamed Nabeel Mattath, and Thimmaiah Govindaraju. They have published a report on their findings in Chemical Communication, a publication of Royal Society of Chemistry.