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How effective is p-chloro-m-xylenol in killing coronaviruses?

Since the outbreak of the new coronavirus, I have been very concerned about the issue of disinfection methods, especially PCMX (parachlorom-dimethylphenol), because I visited a PCMX production workshop in Ningxiang, Hunan a few years ago. I have actually understood the production process and characteristics of this substance. According to the existing evidence, PCMX should have a killing effect on the coronavirus.

PCMX is a broad-spectrum bactericide, which has a relatively strong killing effect on bacteria. I won’t say more about this. What is more worth discussing is how effective it is to kill viruses.

In response to this epidemic, the UTD (UpToDate) database mentioned that “PCMX is not effective against the new coronavirus”, which also caused a lot of controversy more than a month ago. PCMX is the active ingredient of many old-fashioned disinfectants, such as the familiar Dettol, so according to UTD data, it was generally said that Dettol was ineffective against the new coronavirus.

 

But when it comes to Dettol, there is another intriguing detail. The document cited by UTD is a 1998 article [1]. I really went to look for it. The two authors A. Wood and D. Payne. The correspondence address of the latter author is exactly from Dettol. location. The several disinfectants used in the literature are all products of Dettol. There is no doubt that this is a research involving Dettol. Therefore, this quotation becomes, Dettol has done research to prove that its products are invalid… What a straightforward boy!

But the problem is not so simple. Looking carefully at the conclusion of this document, it is still a bit strange. We know that from a structural point of view, viruses can be divided into two types, one is enveloped, such as influenza virus, coronavirus, herpes virus, etc., and the other is without envelope, such as polio virus. , Hand, Foot and Mouth Disease Virus, Hepatitis A Virus and so on.

 

Whether there is a coating or not, the choice of disinfectant makes a big difference. Some disinfectants are only effective against enveloped viruses. For example, medical alcohol can effectively kill enveloped viruses, but it cannot effectively deal with non-enveloped viruses.

Generally speaking, if a disinfectant is effective against a certain virus, it can be inferred that it has an effect on other viruses. For example, this new coronavirus, it was determined from the beginning “56°C for 30 minutes, ether, 75% ethanol…” These methods are effective for viruses because in past experience, they are all effective for viruses with envelopes.

Looking back at the conclusion of this document, it proves that PCMX is effective for viruses with envelopes, but not for viruses without envelopes. It is unique to human coronavirus OC43, which is also an enveloped virus. Causes people to catch a cold, but PCMX is not effective against it.

The matter seems to be over at this point, but this is after all an experiment done before 1998, and the research methods used in the experiment are far behind compared to now. In this document, the virus detection method uses the suspension method to simulate the state of the virus in the cell.

 

Later research found that this method is not suitable for disinfectant application scenarios. Wolff et al. in the book “Coronaviruses with Special Emphasis on First Insights Concerning SARS” proposed that compared to the suspension detection method, QCT-2, which is a quantitative carrier test method, can better reflect the state of the virus when it is disinfected. . The main difference between the suspension method and QCT-2 is that, in simple terms, the suspension method is tested in suspension, while QCT-2 is tested after the surface is loaded. It is not difficult to understand that, we usually disinfect, it is for each Kind of surface rather than suspension.

Using this method to test again, the author found that PCMX is effective against another human coronavirus 229E, which is also a virus that can cause colds in humans.

 

Another key piece of evidence appeared in a 2009 document [2]. The author specifically studied the effects of various household disinfectants on the SARS virus. This is a very necessary work. The SARS virus is a pain in our memory. During the epidemic 17 years ago, although the WHO recommended the use of household disinfectants to disinfect potentially virus-carrying surfaces, we did not have a good weapon at home to deal with it, and we could only rely on it. More corrosive sodium hypochlorite or peracetic acid. However, considering the limitations of the SARS virus and public safety, the researchers chose an alternative virus, that is, MVH virus (mouse hepatitis virus), which is also a type of coronavirus and is closely related to SARS. There are also many similarities in the pathogenesis.

 

The final result confirms [2] that when the concentration of PCMX is adjusted to 0.12%, the effect is 30 seconds, and the logarithmic killing value is above 4, that is, the killing efficiency is above 99.99%. In this way, we can get a basic conclusion that PCMX is still effective against enveloped viruses, and there is no particularity about coronaviruses.

From this research process, it is not difficult to see that our understanding of viruses is gradually changing. The facts we thought in the past will also change with the improvement of technology. Based on this, on February 21, 2020, not long ago, the UTD database has deleted the argument that PCMX cannot kill the new coronavirus.

 

At the same time, the information of the Health Commission is constantly being updated. In the early disinfection recommendations, it was only that “new coronaviruses are sensitive to ultraviolet rays and heat. At 56°C for 30 minutes, ether, 75% ethanol, chlorine-containing disinfectants, lipid solvents such as peracetic acid and chloroform can effectively inactivate the virus.” . In the recent recommendations, “based on previous understanding of the coronavirus, all classic disinfection methods should be able to kill the coronavirus. The World Health Organization…for this new coronavirus, only chlorhexidine is invalid. “In other words, WHO believes that common disinfectants other than chlorhexidine, including PCMX, can be used to disinfect the new coronavirus.

 

However, the existing evidence is only exhaustive and cannot be explained in principle. To thoroughly discuss the killing effect of PCMX on viruses, a core issue needs to be investigated, exactly how PCMX acts on viruses.

 

The full name of PCMX is p-chloro-m-dimethylphenol, and its molecular structure is very symmetrical.

 

 

It should be noted that the “chlorine-containing disinfectant” is mentioned in the materials of the National Health Commission, and PCMX also contains chlorine, so many people initially regarded it as a chlorine-containing disinfectant. But in fact, chlorine-containing disinfectants refer to those substances that use chlorine as an effective ingredient, such as chlorine, sodium hypochlorite, chlorine dioxide, etc., and their killing effects are all marked with “effective chlorine”, while PCMX actually It is a phenolic disinfectant.

 

Phenolic disinfectants are also a classic disinfectant. I learned about phenol in middle school chemistry. One of the practical uses of phenol is that it can be used for disinfection. However, the reputation of phenolic disinfectants is still made by lyso water. Once upon a time, the first feeling when visiting the hospital was the strong smell of lyso water, and lyso water was m-cresol (cresol for short) and A mixture of soap.

 

Because of the classics, the main mechanism of phenolic disinfectants has also been thoroughly studied. The common feature of phenols is that they have a hydroxyl group on the benzene ring. Although many people say that this is “alcohol”, it is still a serious hydroxyl group that can form hydrogen bonds. The secondary structure and tertiary structure of protein are mainly combined by hydrogen bonds, so after protein and phenols meet, they are prone to denaturation and inactivation. So in the laboratory, phenol solution is a classic method of separating proteins.

For bacteria, a large amount of protein is distributed on the cell membrane. Once the protein is denatured, the shape of the cell membrane cannot be maintained, so the phenolic substance has the characteristics of sterilization. This process is like using chopsticks to hold glutinous rice balls. If you are not careful, you can easily break the glutinous rice balls. The same is true for enveloped viruses. After the protein on the envelope is destroyed, the virus that loses its protection is easily inactivated.

 

However, substances such as phenol also have a defect, that is, its water solubility is better, so the damage to the human body will be more obvious, and the higher the concentration will cause corrosion. On the contrary, for viruses, the effect of phenol is not so strong, because the virus envelope is lipophilic.

 

Therefore, one of the improvement directions of phenolic disinfectants is to adjust their hydrophilic and lipophilic properties. For example, PCMX adds two methyl groups and one chlorine more than phenol, and its polarity is greatly reduced. With this dependence, it has a more pronounced killing effect on microorganisms, but has much less toxic and side effects on the human body. Its half lethal dose is more than 3000 mg/kg, which is an order of magnitude with salt. It is basically non-toxic, but its killing efficiency of the virus, as mentioned above, is already very useful at a concentration of 0.12%.

 

To sum up, during the new coronavirus epidemic, the use of PCMX-type disinfection products is still reliable, especially for some people who are prone to allergic exposure to alcohol, the use of PCMX-type household disinfectants will be more gentle. However, it should be mentioned that although the toxicity of PCMX is very low, it does not mean that we can ignore those instructions in the manual. After all, we must consider using it in different scenarios while balancing safety and effectiveness. For example, the representative Dettol, the main products are disinfectant for the surface of the article, disinfectant for the skin, and disinfectant specifically for washing hands, and even for cleaning mucous membranes. So, the disinfectant for different purposes is not recommended. When it is used in disorder and needs to be mixed, it should be carried out in accordance with the recommended concentration in the manual. According to the national standard GB/T 27947-2011 “Phenolic Disinfectants Hygienic Requirements”, the concentration of PCMX should not exceed 2% for surface and skin disinfectant, and should not exceed 1% for hand washing and mucous membranes.

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