In early January 2020, a number of symptoms were attributed to a new coronavirus. The list included fever, cough, muscle and headache pain and, in some cases, loss of taste, smell and severe respiratory symptoms. This characteristic earned it the name of SARS-CoV-2. It is not the first time that members of this family generate respiratory problems: it already occurred with SARS-CoV in 2003 and with MERS-CoV in 2012. However, the pandemic nature of COVID-19 is allowing us to know that the symptoms it is more varied than previously thought.
Even positive patients for the virus without respiratory symptoms, but with other types of problems, have been described. Some examples are stroke, alterations in peripheral circulation, thrombi, hypoxia (less oxygen in the blood) not accompanied by difficulty in breathing, disorientation, delusions and a rare inflammatory pathology such as pediatric multisystemic syndrome, characterized by fever, pain abdominal pain, rashes and accelerated heart rhythms, described in young patients. However, the most common non-respiratory problems are those related to the digestive system, loss of appetite, nausea, and diarrhea.
It is generally accepted that contact or ingestion of animals carrying the virus was the initial route of contagion to humans, as it was with SARS-CoV and MERS-CoV. In the present case, the pangolin is one of the candidates, although it is not something clearly established. It is also unknown whether the virus was able to enter humans in a non-harmful variant, but mutate to a pathogenic one within us.
Receptors: ACE2 and CD147
For a virus to infect us, it is necessary that proteins, called receptors, are found on the surface of some of our cells, which bind to other proteins located in the lipid membrane that surrounds the virus. In this way, the virus can enter and use the cellular machinery to make new virus particles.
So far , two types of receptors have been found in our body that, although they fulfill other functions, can be used by SARS-CoV-2 to infect us.
The first of these is ACE2, which is also the receptor used by the SARS-CoV of 2003. This receptor requires another protein to perform its function: a protease (a protein that breaks down proteins), TMPRSS-2. This in turn, processes another protein that protrudes from the surface of the virus (the Spike or S protein) and that gives it the appearance of a star or crown that gives it its name. After this processing, the viral S protein can be recognized by ACE2 and thus the virus is introduced into the cell.
ACE2 has a wide localization in our organs: from the cerebral cortex and the hypothalamus to the muscle and, although it is present in lung cells, it is not there where it is most abundant. In fact, there is more ACE2 in the testis, kidney, gallbladder, blood vessels, endocrine organs and, especially, in the digestive tract, from the mouth to the rectum, with maximum concentrations in the duodenum and small intestine. This wide distribution is not surprising, since ACE2 performs important physiological functions such as, among others, regulating blood pressure by transforming the vasoconstrictor hormone angiotensin II into the vasodilator angiotensin 1-7.
A ubiquitous molecule
A second recently described receptor is CD147, also called basigin or EMMPRIN (8). CD147 is an important protein for cell recognition, for example, during gametogenesis and the development of the nervous system, as well as for blood group determination. One of its names is due to the fact that it induces the production of proteases that help destroy the extracellular substance, the material that gives consistency to our tissues.
The distribution of this molecule is ubiquitous. It is found in the lungs, but with greater abundance in many other organs such as those of the central nervous system, the endocrine glands, the liver and gallbladder, kidney, pancreas, muscle and, again, especially in the digestive tract. CD147 has an affinity for the same virus surface S protein as ACE2, although it is not yet clear whether both receptors are equally important or whether CD147 is secondary.
In short, SARS-CoV-2 could have, or have had, several routes of entry into our body and, although the respiratory one seems the predominant one, it is not clear that transmission between humans cannot also be varied. Thus, viruses have been found in feces, although their infectivity is disputed.
We still have many unanswered questions. In spite of everything, we have to see the positive side: the virus’s own adaptation to use different pre-existing receptors allows us several approaches to prevent its entry. In fact, trials are already being carried out to block these receptors, assessing, in any case, that the physiological functions they perform are not significantly affected.
Jose Antonio Uranga, Professor of Cell Biology and Histology, Rey Juan Carlos University and Raquel Abalo Delgado, Professor of Pharmacology, Rey Juan Carlos University
This article was originally published on The Conversation. Read the original.
