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The breakthrough at the Eijkman Molecular Biology Research Centre of the National Research and Innovation Agency (BRIN), led by researcher Yudhi Nugraha and his team in Madrid, Spain, has advanced molecular biology to a pivotal point with the creation of Spikebodies. This innovative technology, developed between 2021 and 2023, stands poised to make significant contributions to global health, particularly in combating the SARS-CoV-2 virus.
During the session, Yudhi explained the development and potential of Spikebodies. “We have successfully designed and developed two nanobodies and determined their structures using Cryo-EM,” Yudhi announced. He highlighted a critical step in understanding and manipulating virus behaviour at a molecular level.
The significance of spike proteins was central to Yudhi’s presentation. These proteins are crucial in the context of the pandemic because they facilitate the virus’s entry into human cells by binding to the ACE2 receptor. “Spikebodies are designed to block this interaction between the ACE2 receptor and the SARS-CoV-2 spike, effectively preventing the virus from entering human cells,” Yudhi explained. This blocking is achieved through biotechnological processes, including protein expression, purification, and detailed structural determination using both Cryo-EM and X-ray Crystallography.
Looking ahead, Yudhi shared his strategic vision for the application of nanobody technology: “Our next strategic target is to utilise this technology to prevent all types of viruses through adaptation to structural differences in key proteins responsible for transmission.”
In stressing the role of structural biology, Yudhi discussed how this field is pivotal for unlocking the mysteries of molecular biodiversity. The Cryo-EM technology at BRIN, for instance, allows researchers to visualise structures at an atomic level, providing a deep understanding of biological mechanisms and pathways.Cryo-EM is a method that determines the 3D structures of biomacromolecules, such as proteins and nucleic acids, by imaging them at cryogenic temperatures.
Yudhi said this research not only sheds light on fundamental biological processes but also paves the way for the development of targeted medical interventions such as drugs, antibodies, and nanobodies. “Cryo-EM technology allows us to see and understand the machinery of viruses at a molecular resolution, which is crucial for developing effective strategies against viruses like SARS-CoV-2,” he stated.
Yudhi also elaborated on how the structural biology approach aids in understanding the transmission mechanisms of viruses, thereby enabling researchers to design antibodies that are finely tuned to combat viruses effectively. “By deciphering the virus’s structure, we gain insights into its interaction patterns and lifecycle within the host cell, which is instrumental in crafting potent antibodies,” he explained.
Moreover, this approach’s adaptability is key, especially as viruses evolve. “Even when the virus mutates to evade the existing immune defences, we can quickly adapt by designing new nanobodies that are effective against the mutated variants,” Yudhi noted.
This deep dive into the structural understanding of molecules is foundational in the field of structural biology, which stands at the forefront of designing proteins that can meet specific health needs and address particular biological challenges.
Yudhi believed that the development of Spikebodies represents a significant leap forward in the ongoing battle against pandemics. Harnessing cutting-edge technologies like Cryo-EM is not only advancing the fundamental understanding of virus behaviour but also developing innovative tools to mitigate these threats effectively. “This integration of digital technology and molecular biology illustrates the powerful synergy that can lead to transformative solutions in global health security,” Yudhi asserted.