Naukovi Novyny, Vol 2, Issue 4, April 30, 2020
ACE2, spikes, hydroxychloroquine and dogs
ACE2, spikes, hydroxychloroquine and dogs
D. Demydenko (editor)
D. Demydenko (editor)
As of April 29, 2020, about 3 million people were diagnosed with COVID-19 (COrona VIrus Disease 2019) and about 200 thousands died with the diagnosed presence of coronavirus SARS-CoV-2 (also known as 2019-nCoV) [1].
As of April 29, 2020, about 3 million people were diagnosed with COVID-19 (COrona VIrus Disease 2019) and about 200 thousands died with the diagnosed presence of coronavirus SARS-CoV-2 (also known as 2019-nCoV) [1].
The cell surface receptor protein or "lock" or "gate" through which SARS-CoV-2 enters cells is called ACE2 (angiotensin-converting enzyme 2). One part of ACE2 is an enzyme that cuts off the terminal components of some protein molecules, such as angiotensin, to function in deactivating them. But this is not the only ACE2 function, as it interacts not only with angiotensin, and it also has another part that performs the function of transporting certain molecular components. In general, the function of ACE2 is not fully known. In the human body, ACE2 is present in the kidneys, lungs, gastrointestinal tract, brain [2] and, according to some unconfirmed data, on the inner surface of the nasal cavity. Multifunctionality, due to the above mentioned features, is the basis for ACE2 involvement, among other things, in the regulation of blood pressure, metabolism in the kidneys and lungs, heart and the central nervous system function [2].
The cell surface receptor protein or "lock" or "gate" through which SARS-CoV-2 enters cells is called ACE2 (angiotensin-converting enzyme 2). One part of ACE2 is an enzyme that cuts off the terminal components of some protein molecules, such as angiotensin, to function in deactivating them. But this is not the only ACE2 function, as it interacts not only with angiotensin, and it also has another part that performs the function of transporting certain molecular components. In general, the function of ACE2 is not fully known. In the human body, ACE2 is present in the kidneys, lungs, gastrointestinal tract, brain [2] and, according to some unconfirmed data, on the inner surface of the nasal cavity. Multifunctionality, due to the above mentioned features, is the basis for ACE2 involvement, among other things, in the regulation of blood pressure, metabolism in the kidneys and lungs, heart and the central nervous system function [2].
That is, SARS-CoV-2, using the "key", its spike glycoprotein, can penetrate wherever ACE2 is present and directly or indirectly disrupt the functioning of many organs of the human body [3].
That is, SARS-CoV-2, using the "key", its spike glycoprotein, can penetrate wherever ACE2 is present and directly or indirectly disrupt the functioning of many organs of the human body [3].
Schematic illustration of SARS-CoV-2 (Centers for Disease Control and Prevention (CDC), USA)
The structure of the “key” of SARS-CoV-2, or its spike glycoprotein, was recently determined [4]. Its ability to bind to ACE2 was also measured. It turned out to be 10-20 times higher than the ability to bind to ACE2 of the spike glycoprotein of the SARS-CoV-1 virus [4], which caused the 2003-2004 SARS epidemic. This may explain the much higher infectivity of SARS-CoV-2.
The structure of the “key” of SARS-CoV-2, or its spike glycoprotein, was recently determined [4]. Its ability to bind to ACE2 was also measured. It turned out to be 10-20 times higher than the ability to bind to ACE2 of the spike glycoprotein of the SARS-CoV-1 virus [4], which caused the 2003-2004 SARS epidemic. This may explain the much higher infectivity of SARS-CoV-2.
The percentage of fatal cases (approximately 6%) indicates that most people's defense mechanisms successfully cope with the infection. Although perhaps some role is played by the fact that the structure of ACE2 is somewhat different in different people and in some people SARS-CoV-2 easily penetrates into cells and in others penetrates much worse or does not penetrate at all. Genetic differences between people and differences between the health state of different people most likely are also the reasons of problems related to search for therapeutic approaches for treatment of COVID-19 [5].
The percentage of fatal cases (approximately 6%) indicates that most people's defense mechanisms successfully cope with the infection. Although perhaps some role is played by the fact that the structure of ACE2 is somewhat different in different people and in some people SARS-CoV-2 easily penetrates into cells and in others penetrates much worse or does not penetrate at all. Genetic differences between people and differences between the health state of different people most likely are also the reasons of problems related to search for therapeutic approaches for treatment of COVID-19 [5].
With regard to therapeutic approaches, many physicians have paid attention to hydroxychloroquine [6], which is a mild immunosuppressant, that is, it suppresses the immune system and may be useful when the immune response to SARS-CoV-2 infection is too strong and the immune response can be lethal. But some people confuse hydroxychloroquine and chloroquine [7], which is much more toxic to the human body.
With regard to therapeutic approaches, many physicians have paid attention to hydroxychloroquine [6], which is a mild immunosuppressant, that is, it suppresses the immune system and may be useful when the immune response to SARS-CoV-2 infection is too strong and the immune response can be lethal. But some people confuse hydroxychloroquine and chloroquine [7], which is much more toxic to the human body.
Hydroxychloroquine, like chloroquine, does not have a well-defined target in the human body. It acts on many components of the human body, having for the most part the overall toxicity felt first by the immune system due to the complexity of the immune systems mechanisms of functioning. This is the reason for its use as an immunosuppressant.
Hydroxychloroquine, like chloroquine, does not have a well-defined target in the human body. It acts on many components of the human body, having for the most part the overall toxicity felt first by the immune system due to the complexity of the immune systems mechanisms of functioning. This is the reason for its use as an immunosuppressant.
More successful therapeutic agents are those that selectively affect the components of the virus. The search for such therapeutic agents is often conducted through the identification of three-dimensional structures of the components of the virus and the subsequent selection and synthesis of chemical compounds that could block the function of these structures. The determination of the structure of the spike glycoprotein of SARS-CoV-2 was mentioned above. The structure of the SARS-CoV-2 protease was also determined and published this month [8]. These decoded structures will accelerate the search for drugs for targeted anti-SARS-CoV-2 therapy.
More successful therapeutic agents are those that selectively affect the components of the virus. The search for such therapeutic agents is often conducted through the identification of three-dimensional structures of the components of the virus and the subsequent selection and synthesis of chemical compounds that could block the function of these structures. The determination of the structure of the spike glycoprotein of SARS-CoV-2 was mentioned above. The structure of the SARS-CoV-2 protease was also determined and published this month [8]. These decoded structures will accelerate the search for drugs for targeted anti-SARS-CoV-2 therapy.
The ability of dogs to detect the pathogen Liberibacter asiaticus of the Citrus trees was experimentally demonstrated this month [11]. Disease of the Citrus trees named Huanglongbing (HLB), caused by the Liberibacter asiaticus, is the most widespread modern pandemic disease of citrus plants.
The ability of dogs to detect the pathogen Liberibacter asiaticus of the Citrus trees was experimentally demonstrated this month [11]. Disease of the Citrus trees named Huanglongbing (HLB), caused by the Liberibacter asiaticus, is the most widespread modern pandemic disease of citrus plants.
Used sources:
Used sources:
1. Google.com (https://news.google.com/covid19/map?hl=uk&gl=UA&ceid=UA:uk)
1. Google.com (https://news.google.com/covid19/map?hl=uk&gl=UA&ceid=UA:uk)
2. ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models. Alenina N, Bader M. Neurochem Res. 2019 Jun;44(6):1323-1329. doi: 10.1007/s11064-018-2679-4. Epub 2018 Nov 15. Review (https://link.springer.com/article/10.1007/s11064-018-2679-4).
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3. A rampage through the body. Wadman M, Couzin-Frankel J, Kaiser J, Matacic C. Science. 2020 Apr 24;368(6489):356-360. doi: 10.1126/science.368.6489.356. (https://science.sciencemag.org/content/368/6489/356/tab-pdf)
3. A rampage through the body. Wadman M, Couzin-Frankel J, Kaiser J, Matacic C. Science. 2020 Apr 24;368(6489):356-360. doi: 10.1126/science.368.6489.356. (https://science.sciencemag.org/content/368/6489/356/tab-pdf)
4. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Science. 2020 Mar 13;367(6483):1260-1263. doi: 10.1126/science.abb2507. Epub 2020 Feb 19. (https://science.sciencemag.org/content/367/6483/1260)
4. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Science. 2020 Mar 13;367(6483):1260-1263. doi: 10.1126/science.abb2507. Epub 2020 Feb 19. (https://science.sciencemag.org/content/367/6483/1260)
5. How does COVID-19 kill? Uncertainty is hampering doctors' ability to choose treatments. Ledford H. Nature. 2020 Apr;580(7803):311-312. doi: 10.1038/d41586-020-01056-7. PMID: 32273618 DOI: 10.1038/d41586-020-01056-7 (https://www.nature.com/articles/d41586-020-01056-7)
5. How does COVID-19 kill? Uncertainty is hampering doctors' ability to choose treatments. Ledford H. Nature. 2020 Apr;580(7803):311-312. doi: 10.1038/d41586-020-01056-7. PMID: 32273618 DOI: 10.1038/d41586-020-01056-7 (https://www.nature.com/articles/d41586-020-01056-7)
6. Hydroxychloroquine (https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxychloroquine).
6. Hydroxychloroquine (https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxychloroquine).
7. Chloroquine (https://pubchem.ncbi.nlm.nih.gov/compound/chloroquine).
7. Chloroquine (https://pubchem.ncbi.nlm.nih.gov/compound/chloroquine).
8. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020 Apr 24;368(6489):409-412. doi: 10.1126/science.abb3405. Epub 2020 Mar 20. Zhang L1,2, Lin D1,3, Sun X1,2, Curth U4, Drosten C5, Sauerhering L6,7, Becker S6,7, Rox K8,9, Hilgenfeld R10,2 (https://science.sciencemag.org/content/368/6489/409).
8. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020 Apr 24;368(6489):409-412. doi: 10.1126/science.abb3405. Epub 2020 Mar 20. Zhang L1,2, Lin D1,3, Sun X1,2, Curth U4, Drosten C5, Sauerhering L6,7, Becker S6,7, Rox K8,9, Hilgenfeld R10,2 (https://science.sciencemag.org/content/368/6489/409).
9. Medical Detection Dogs is looking into whether man’s best friend could play a role in preventing the spread of Coronavirus. Благодійна організація Medical Detection Dogs (https://www.medicaldetectiondogs.org.uk/covid-19-dogs/)
9. Medical Detection Dogs is looking into whether man’s best friend could play a role in preventing the spread of Coronavirus. Благодійна організація Medical Detection Dogs (https://www.medicaldetectiondogs.org.uk/covid-19-dogs/)
10. Bio Detection Dogs, Благодійна організація Medical Detection Dogs (https://www.medicaldetectiondogs.org.uk/about-us/bio-detection-dogs/).
10. Bio Detection Dogs, Благодійна організація Medical Detection Dogs (https://www.medicaldetectiondogs.org.uk/about-us/bio-detection-dogs/).
11. Canine olfactory detection of a vectored phytobacterial pathogen, Liberibacter asiaticus, and integration with disease control. Gottwald T, Poole G, McCollum T, Hall D, Hartung J, Bai J, Luo W, Posny D, Duan YP, Taylor E, da Graça J, Polek M, Louws F, Schneider W. Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3492-3501. doi: 10.1073/pnas.1914296117. Epub 2020 Feb 3 (https://www.pnas.org/content/117/7/3492).
11. Canine olfactory detection of a vectored phytobacterial pathogen, Liberibacter asiaticus, and integration with disease control. Gottwald T, Poole G, McCollum T, Hall D, Hartung J, Bai J, Luo W, Posny D, Duan YP, Taylor E, da Graça J, Polek M, Louws F, Schneider W. Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3492-3501. doi: 10.1073/pnas.1914296117. Epub 2020 Feb 3 (https://www.pnas.org/content/117/7/3492).