A Chinese study showed that in the early stage of infection with the new covid strain, the high temperature in the human body may reduce the combination of the new coronavirus and human cells to a certain extent, thereby delaying the infection of the virus to the human body and reducing the viral load in the patient overall. After the human body is infected with the virus, it sometimes provokes people to have a strong response, such as a high fever. The study was recently published in the Journal of Computational and Structural Biotechnology (CSBJ) and was led by a team from Jinan University, Guangzhou Guangdong Laboratory of Regenerative Medicine and Health, Shenzhen Chengqi Biotechnology, and Southern Medical University.
Today, the average body temperature is between 36.5 and 37 °C, and the general definition of high fever is more than 38 °C. After this phenomenon occurs, in order to avoid organ failure caused by persistent high fever, people usually undergo corresponding treatment to lower body temperature immediately after the detection of high fever. The new coronavirus relies on the S protein on its surface to bind to the ACE2 receptor on the surface of human cells, which in turn invades the cell. The study found that at relatively high body temperatures, the binding affinity of the S protein on the surface of the new coronavirus with the ACE2 receptor of human cells was greatly weakened. The research team calculated this phenomenon using molecular dynamics simulation and surface plasmon resonance analysis, which was further confirmed with a fake viral infection experiment.
According to the study, the nucleic acid test results of clinical samples showed that patients with a body temperature below 38 °C in the early stage of new corona infection had a viral load in their bodies far exceeded those with a body temperature above 38 °C. In the early stages of infection, a higher body temperature can effectively slow down the rate at which the new coronavirus infects human cells, giving the body more time to mobilize the immune system to deal with the virus, resulting in milder symptoms and lower mortality. In the late stage, because the new coronavirus has been widely infected in the body, causing serious cytokine storms and complications, the advanced high temperature can only bring damage to the human body, but cannot kill the virus. Zhang Gong, the corresponding author of the paper and a researcher at the School of Life Science and Technology of Jinan University, told 财新网 that the initial stage of infection is generally at the time of admission and a short period of time after admission, and the late-stage refers to the occurrence of serious complications and cytokine storms. The link to the original content is given at the end of this article (available in Mandarin).
The team's in vitro experimental results showed that at 40 °C, the amount of new coronavirus that invaded cells in 24 hours was only one percent of what it was at 37 °C. That is to say, the binding affinity of the new coronavirus to the ACE2 receptor of human cells is much lower at 40 °C than at 37 °C. In Physio-chemistry, the strength of affinity is expressed by the equilibrium dissociation constant (KD, nanomole/L per liter), and in general, the smaller the value of the dissociation equilibrium constant, the stronger the affinity. However, a fever of 40 °C is extremely rare for adults. Zhang Gong told the 财新网 reporter that in terms of the binding affinity of the experimental results, the equilibrium dissociation constant at 38 °C is significantly larger than that of 37 °C, indicating that the binding affinity of the new coronavirus and human cells at 38 °C has dropped dramatically.
On the other hand, although fever is a normal response of the human body to foreign pathogenic microorganisms, in terms of coping with coronaviruses, fever does not permanently inhibit the infection of coronaviruses. As far as the SARS virus is concerned, the binding force with ACE2 at high temperature does not weaken, that is, its infectivity at high temperature does not weaken. This difference stems from the different structures of the receptor-binding domain (RBD) of the spike proteins on the surface of the two coronaviruses. Therefore, the temperature characteristics at the time of binding to ACE2 are very different. At high temperatures, the RBD domain of the SARS virus is relatively tight and maintains good binding energy. The RBD domain of the new coronavirus is relatively loose, and the binding energy is low.
However, it is worth noting that the difference in the temperature of the host body between the two coronaviruses is not a simple variation from only a few amino acids in the RBD domain. A previous clinical data analysis study of 2300 patients showed that the new crown virus and the SARS virus stimulate the human immune system in a very different way: the new coronavirus has a weak stimulation of the immune system in the early stage of infection, so it is relatively less likely to cause high fever immediately so that it remains highly infectious and infectious to the body; The SARS virus strongly stimulates the immune system in the early stage of infection, causing high fever, and under the premise of no weakening of binding, the high temperature is conducive to the spread of the SARS virus in the body, resulting in the SARS virus infecting more cells as soon as possible.
This article is from the originally paid website "财新网", a contribution towards educational purposes. Click at the end of the article to read the full text, available in Mandarin.
www.xueqiu.com; author: 财新健康
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