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A recent study from Belize and Taiwan shows that four essential proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are well adapted to habitable temperatures and exhibit extreme thermostability, which means that temperature changes between winter and summer months have a negligible effect on viral spread. The document is currently available on the bioRxiv * pre-print server.
The evolution of SARS-CoV to SARS-CoV-2, with the subsequent emergence of coronavirus disease 2019 (COVID-19), involves a complex and beneficial evolutionary interaction that has created a perfect storm for the rise of the pandemic In progress.
So far, the global infection rate has undoubtedly demonstrated that SARS – CoV-2 is quite stable when exposed to cold and hot temperatures. Therefore, the initial hopes of a strict viral seasonality were not supported by epidemiological data.
However, the effects of temperature on the receptor binding domain (RBD) of the spike glycoprotein, the major protease (Mpro), macrodomain X (Macro X) and the core protein remain uncertain and require further investigation. urgent clarification as to their potential for stability. drug targets.
This prompted Dr Paul Morgan from the Faculty of Science and Technology, University of Belize, Belmopan City, Belize, and Dr Chih-Wen Shu from National Sun Yat-Sen University, Kaohsiung, Taiwan , to investigate this intriguing question. in depth.
Molecular dynamics simulations
In this study, the research duo used molecular dynamics simulations to assess the effect of temperature on these four critical proteins – SARS-CoV-2 RBD, Mpro, Macro X and the nucleocapsid. The temperature used ranged from -18 ° C to 49 ° C.
In addition, they investigated the effect of temperature on the root mean square fluctuation (RMSF) of critical residues in RBD, which are ultimately responsible for initiating the interaction with angiotensin-converting enzyme 2 (ACE -2) – the entry point for infection of lung cells.
However, it should be noted that their research approach had several practical limitations. As there are a myriad of proteins in SARS-CoV-2, the assessment is not exhaustive and it is not easy to simulate changes in humidity using molecular dynamics simulations (despite its close relationship with temperature).
Four key proteins of SARS-CoV-2 are thermostable
“Our results suggest that RBD, Mpro and Macro X are inherently thermostable, making them ideal drug targets with potentially desirable drug binding kinetics,” say the authors of this study. “This is because secondary structural changes are often a consequence of inhibitor binding,” they add.
In addition, it should be noted that the nucleocapsid exhibited the lowest average kinetic energy in the entire temperature series, while Mpro had the highest average kinetic energy. On the other hand, RBD and Macro X displayed comparable kinetic energy and were in fact the least reactive when subjected to the series of experimental temperatures.
Finally, the high stiffness, thermal stability, and decreased flexibility observed in the SARS-CoV-2 subregion of RBD may be the driver for the substantial increase in affinity for ACE-2, with far-reaching implications.
Negligible effect on transmissibility
The implications of our study suggest that four essential proteins of SARS-CoV-2 are well adapted to inhabitable temperatures on earth and exhibit extreme thermo-stability, ”warn the authors of this study. bioRxiv paper.
As a result, a negligible effect on the transmissibility of SARS-CoV-2 (with respect to temperature changes between the winter and summer months) was noted, resulting in a marginal effect on the rates. transmission until strong drugs are available.
More importantly, this study actually created a basic framework for unveiling promising stable drug targets for SARS-CoV-2. Nonetheless, we understand that the coronavirus machinery is extremely complex, with potentially many other stabilization mechanisms and protein-protein interactions that are used to cope with environmental stressors.
*Important Notice
bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as established information.
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