Researchers have identified a novel pathway to advance the understanding of the Monkeypox Virus (MPV) and create innovative diagnostic tools, offering fresh therapeutic possibilities. Known as Mpox, the virus has been declared a Public Health Emergency of International Concern (PHEIC) twice in the past three years due to its sudden and widespread outbreaks. With global transmission patterns and symptoms still poorly understood, scientists stress the urgency of developing effective diagnostic and treatment strategies.
MPV, a double-stranded DNA (dsDNA) virus, is typically identified in clinical samples using polymerase chain reaction (PCR). While PCR is a reliable method for detecting dsDNA, its fluorescent probes cannot differentiate between specific and non-specific amplification products, leading to potential inaccuracies. However, researchers have proposed using unconventional DNA structures as diagnostic targets to address these limitations.
The molecular probe BBJL sets a benchmark in targeting noncanonical nucleic acids for MPV detection
Thimmaiah Govindaraju
One such DNA structure is the G-quadruplex (GQ), a unique noncanonical conformation found in guanine-rich nucleic acid sequences. GQs form planar tetrads through hydrogen bonding among guanines, stacking to create a stable configuration. These structures deviate from the classical double helix and have shown promise as targets for small-molecule fluorescent probes. By leveraging these unusual structures, scientists aim to develop precise diagnostic assays for MPV.
A research team from Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), under the Department of Science and Technology (DST), has identified highly conserved GQ-forming sequences in the MPV genome. Their study pinpointed four specific GQ sequences that are stable under physiological conditions, absent in other pox viruses, and distinct from the human genome. These unique features make them valuable targets for diagnostic tools and therapeutic interventions.
Using a custom-designed small-molecule fluorescent probe called BBJL, the researchers successfully detected one of these conserved GQ sequences, enabling highly accurate identification of MPV. The probe exhibited a more than 250-fold fluorescence enhancement when bound to the MPV GQ structure, demonstrating exceptional sensitivity and specificity. “The molecular probe BBJL sets a benchmark in targeting noncanonical nucleic acids for MPV detection,” said lead researcher Thimmaiah Govindaraju.
Notably, the probe remains non-fluorescent in the absence of its target GQ-DNA, ensuring minimal false positives. This development represents the first practical application of a GQ-targeted diagnostic strategy for detecting MPV. The team’s approach expands upon their earlier GQ-targeted diagnostic platform, GQ-RCP, originally designed for SARS-CoV-2 detection. Their findings, previously published in ACS Sensors, underscore the versatility and potential of GQ-based diagnostics.
This study bridges the gap in MPV virology by introducing a molecular-level solution with diagnostic and therapeutic implications
Sumon Pratihar
Beyond diagnostics, the identified GQs could serve as antiviral targets, opening new therapeutic avenues. Mapping the MPV genome further to uncover additional GQ targets could bolster the development of advanced antiviral treatments. By targeting these unique nucleic acid structures, researchers hope to achieve significant breakthroughs in the fight against MPV.
The implications of this research are profound. Conventional diagnostic methods, such as amplification-based techniques, often struggle with non-specific amplification, leading to false-positive results. GQ-targeted probes like BBJL address this challenge by offering unparalleled specificity. “This study bridges the gap in MPV virology by introducing a molecular-level solution with diagnostic and therapeutic implications,” noted co-researcher Sumon Pratihar.
The broader scientific community stands to benefit from this discovery. The identified GQs not only enhance the precision of MPV detection but also pave the way for investigating their potential antiviral properties. These molecular probes could revolutionize how virologists and healthcare professionals approach MPV, ultimately improving patient outcomes and advancing global public health.
As research progresses, scientists aim to refine this technology and explore its applications in detecting other pathogens with unique DNA structures. By prioritizing precision and reliability, this approach could redefine diagnostic and therapeutic practices, addressing the ongoing challenges of infectious disease outbreaks.
(Input from various sources)
(Rehash/Yash Kamble/MSM)
