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The new coronavirus was first identified in patients with pneumonia of unknown cause in Wuhan, China, in late December 2019. The cases were caused by the new pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV). -2), which has now spread all over the world. More than 40 million cases of SARS-CoV-2 infection have been reported, leading to more than 1 million deaths. Mitigation of this infection requires immediate effective therapeutic drugs.
To do this, it is essential to understand the virus and its mechanisms. Recently, the inactivation of the virus to contain its spread has become the goal of researchers from various disciplines. Treatment methods employing chemical, biological and physical strategies are being used to slow this viral spread. While SARS-CoV-2 is reported to be very stable at low temperatures (i.e. 4 ° C up to 14 days), it is known to be heat sensitive.
Didac Marti et al., from the Polytechnic University of Catalonia, in a recent bioRxiv* Pre-printed research paper, explores the effect of temperature on the molecular structure of the SARS-CoV-2 peak glycoprotein. The study specifically focuses on the molecular structural integrity of the peak glycoprotein at different temperatures (between 25ºC and 100ºC) using atomistic computer simulations.
Both of them closed Y open The states, which determine the accessibility to the receptor-binding domain (RBD), were considered. The study results suggest that the drastic change in hydrogen bonding (H bonding) inactivates the virus, and intact salt bridges in the protein retain the macrostructure of the peak.
The SARS-CoV-2 virus uses the spike glycoprotein, a homotrimer with three monomers, called the A, B and C chain, to bind to host cellular receptors (human angiotensin converting enzyme 2 (ECA2). This triggers a cascade of reactions, resulting in viral entry into the host.
In this study, atomistic Molecular Dynamics (MD) simulations were performed on this homotrimeric protein in an aqueous solution. Both of them closed Y open The conformational states of the protein were studied. the closed the state is when the receptor binding to interact with ACE2 is hidden; the open The state is when the receptor binding motifs are exposed.
MD is a computational tool that captures time-dependent conformational changes under various conditions. Calculates the interatomic forces through a solvent, providing the underlying dynamics of the specific molecule.
The Protein Data Bank (PDB) is the source of the atomic coordinates of the homotrimeric spike glycoprotein of SARS-CoV-2 in both conformational states.
Although this study does not delve into the energetics of the different conformations, the authors observe that the closed conformational state stabilizes. This order of stability is also observed in experiments. Thermally induced structural distortions are more pronounced for the open state.
The authors report that temperature affects the peak glycoprotein, which inactivates the virus after a certain threshold. Changes in temperature induce a remodeling of the internal network of hydrogen bonds. Significantly, this affects the recognition functionality of the receptor-binding domain.
In contrast, the topology of the salt bridge remains practically unchanged. The macrostructure of the spike is thus preserved at high temperatures due to the retained salt bridges. This study analyzes a detailed analysis of the temporal evolution of the structural conformation at different temperatures. The proposed mechanism has important implications for designing new approaches to inactivate the SARS-CoV-2 virus.
MD is the best methodology to discover atomic interactions in silico uncover a molecular mechanism for virus inactivation; conducting this study experimentally in a physical laboratory is challenging. However, the insights from the study contribute greatly to the development of new strategies to disable the functional sites of the virus, allowing effective mitigation steps to control the spread of the infection.
The authors call for new strategies to inactivate SARS-CoV-2 using chaotropic agents and surfactants or through physical treatments to selectively target such labile hydrogen bond structures.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
