Coronaviruses: Who ate a bat?

In the second video lecture from the series “Coronavirus: New Data” [ 1 ], read on April 11, Professor Penovov emphasized how important it is to diagnose the asymptomatic carriage of coronavirus. He spoke about the taxonomy of the coronavirus family and compared the mortality of the new virus with those that previously caused epidemics of atypical pneumonia, “pork” and ordinary seasonal flu.

In addition, the lecturer draws attention to the fact that over the past two months the epidemiological situation in the world has changed very much. At the time of delivery of the number to print, the number of identified cases of the disease reached 2.5 million. More than 165 thousand dead, according to official estimates, and these numbers are growing noticeably every day.

In the current epidemiological situation, it is important for people to obtain objective information - it allows you to consciously apply security measures. Then we have a chance if not to defeat this epidemic, then at least it is to minimize its consequences. But for starters, I would like to recall some information about coronaviruses. They were opened in the mid-1960s. When virologists first saw a viral particle in an electron microscope, they thought that its shape was most reminiscent of the sun with a sunny crown. That is why such particles were called coronaviruses.

Let's look at the structural model of coronavirus. It can be seen that this virus has a lipid shell. In this lipid shell there are built -in three types of proteins, which, in fact, form a crown. The first of them is the protein of spikes, or, in English, a spike-bead, it can also designate it with the letter S. It really creates a shell and forms a semblance of a halo around the virus. Further, the membrane of the Bite of the E and the membrane M-Beach, which play very little beyond the boundaries of the lipid membrane, are built into the membrane, and it is not yet clear what role they play in the production of immunity for this virus. Finally, inside the lipid shell is genomic RNA in combination with Nucleoprotein protein - N. This protein is the most massive protein of the viral particle.

It is important to note that the genome of this virus is the largest among RNA-containing viruses. In coronaviruses, its dimensions range from 27 to 32 thousand nucleotides. As for RNA viruses, it is a person, the dimensions of their genomes are approximately 29 thousand nucleotides. We see that several proteins are encoded here - no less than, for example, in the tick -borne encephalitis or enterovirus virus.

In the structure of the alpha-coronavirus genome, 229e and beta-coronavirus of mouse hepatitis (Fig. 2) can be seen two very large proteins: 1a and 1b [2]. This is RNA polymerase of the virus with two different functions. One of them is directly related to the reproduction of viruses, as it propagates viral ribonucleic acid. The second polymerase synthesizes the matrix RNA in various areas of the genome, so that viral proteins synthesize on their matrices.

Taxonomy of coronaviruses

The family of coronaviruses consists of two subfamily, and only one of them, Orthocoronavirinae, include coronaviruses (Fig. 3). This subfamily consists of four births: alpha, beta, gamma, delta, and each of the birth also has toogrades. We are only interested in two kinds: this is Alphacoronavirus and Betacoronavirus . The genus of alpha-koronaviruses includes two coronavirus of a person who cause ordinary colds and have been known since the 1960s. Beta-koronaviruses include two ordinary coronavirus of a person and, in addition, those three varieties of coronaviruses that have caused epidemics in the world over the past 20 years.

I must say that the subfamily of coronaviruses turned out to be very extensive: coronaviruses cause infections, sometimes quite serious, in pigs, horses, dogs, cats, bats, different types of ordinary mice, rats, other rodents, marchings, pancakes, pangolins, hedgehogs, birds, whales-whitewashes, etc. This has long caused the need to develop a long time ago. Vaccines against coronavirus infections of those animals that we really need: we use them in food or as pets.

Among the last coronaviruses, the SARS-COV-1 is known primarily-atypical pneumonia virus 2002-2003. In Russian it is called torso coronavirus: a virus of severe acute respiratory syndrome. The next was the virus of the Middle Eastern respiratory syndrome, or Mers-Koronavirus. It was discovered in 2012 in Saudi Arabia, passed to a person from camels. Unfortunately, the virus continues to circulate now, but only in very few countries where there are rosett bats and camels. Finally, Sars-Cov-2 is the name of the current coronavirus. It does not need to be confused with the name of the disease-Covid-19: the name of the disease is claimed by the World Health Organization, and the name of the virus-the International Committee for Tuirus Taxonomy.

Virus behavior in nature

Speaking of past outbreaks, one must understand the scale of the epidemic. Torsonavirus led to more than eight thousand cases of disease and 770 deaths in about 33 countries. And since 2012 the virus of the Middle Eastern respiratory syndrome has already caused more than two and a half thousand cases. Mortality from it is much higher - more than 800 people died from the consequences of infection with this virus. Let's look at the clinical manifestations of the atypical pneumonia virus, which are already firmly established (and there are certain ratios of these forms) and which are also characteristic of the current coronavirus.

The first form of manifestation is an asymptomatic, or soft respiratory disease , which a person most often does not feel or almost does not notice. At the same time, the patients distinguish viruses and are distributors, especially since they are not placed, as a rule, to the hospital. Therefore, they need to pay close attention to them, especially when we know that the virus is very contagious and its distribution coefficient is quite large.

The second species is a moderate course . At the same time, people, as a rule, tolerate the disease at home or in ordinary wards of a regular hospital.

The third form is a serious respiratory disease with pneumonia (inflammation is first viral, then a bacterial infection joins it). It is these patients that should be treated in intensive care rooms, which are now crowded around almost the whole world.

The forms of manifestation of the current infection have not yet been sufficiently studied, but judging by the percentage of the sick, by gravity and course, by individual clinical signs, the picture by 90% looks the same as with atypical pneumonia of 2002-2003.

We know that the virus of the Middle Eastern respiratory syndrome (Mers-Coronavirus) at first met only in Saudi Arabia. There, vigilance was shown by one doctor who realized that he sees something unusual, and sent samples to the European Center for the Study of Coronaviruses and other respiratory viruses in Rotterdam. Pretty quickly he received an answer, and then diagnostic test systems were developed for this disease, and then retrospective studies were also done. As a result, it turned out that this virus appeared in the human population no later than 2007, and then it caused only isolated cases of the disease. And the first significant outbreak occurred only in 2012. When they studied the nature of this disease, it turned out that mostly people received it from camels, who were sick almost asymptomatic and at the same time were chronic carriers of the virus. Only in a few cases, Mers was not associated with camels when people were in contact with those who were already sick.

I must say that this disease could not be eradicated, because for this it would be necessary to eradicate camels. At first, they thought that it was possible to eradicate bats, from which the infection passed to camels, but it is difficult to even catch the bats there. And then, in nature there are a lot of them. Therefore, it is easier to protect camels. It was for camels that they began to develop a vaccine, which, as far as I know, is now undergoing clinical trials in the countries of the Arabian Peninsula.

From December 2012 to January 9, 2020, the World Health Organization received data on 2494 laboratory confirmed cases of MERS infection, of which 858 (34.4%) ended with fatal outcome. It is clear that the disease is very serious and, of course, it is worth developing a camel vaccine so that people do not become infected from them. The camels that carry the disease are one -humped, they live far from everywhere, and at least for now, do not worry about those countries where there are only two -humped camels.

Covid-19: How do we get

If you look at the dynamics of incidence in the world with the new coronavirus SARS-COV-2 [ 3 ], it is clear that the curve is still exponential in nature, despite the fact that China where this virus arose has almost overcome the outbreak. Now the increase in the number of cases is mainly due to Western Europe, the USA and some other countries where the infection is only gaining momentum. Russia is now in fact at the beginning of the epidemic (not even in the middle), because the number of cases is growing daily. I must say that the quarantine that is introduced in our country is not useless, because on the collectible translation of this virus on average it takes from 7 to 14 days, sometimes less or more, and therefore quarantine measures will begin to affect only 2 weeks after their introduction. We will have to patient and wait to see the results of quarantine.

To the history of our time of our time

By January 10, ten Covid-19 genomes were sequenced. It was shown that these genomes are most homologous to the viruses of bats, and this homology reaches approximately 90%. Moreover, the viruses themselves, allocated from a person, are only slightly different from each other. But they are very much, by about 20%, differ from the atypical pneumonia virus of 2002-2003. This suggests that the current virus did not arise from the same bats, and it did not arise from that old virus. Covid-19 is a new virus, and this knowledge will come in handy to us later. Since the differences between viruses allocated from different people are very small, the primary source of infection was, most likely, only one patient .

The following figures will help to present the scale of the research work, which is now being conducted in the world: more than 2200 genomes of different insulators from people, several hundred new isolates from bats and several isolates from various animals have already been sequenced. Initially, it was believed that the Pangolins were intermediate hosts on the path of the bats virus to a person. But now a few more hypotheses are nominated, because it turned out that cats or dogs can also be intermediate masters. Why couldn't this be found out at once? Because as soon as they learned that the infection occurred in the market or near it, this market was not just eliminated - it was immediately literally destroyed with all the animals and other organisms that were there.

In Fig. 4 shows a generalized phylogenetic tree of the subfamily coronaviruses. Different colors indicate different genera. The current SARS-COV-2 virus belongs to the family of beta-koronaviruses. The stars indicate modern isolates that were highlighted during the current epidemic. In the same branch-the isolates of the atypical pneumonia virus (TOPC-coronavirus), but they are not particularly close to the current coronavirus-only about 80% of identical nucleotides; And the isolates of the camel coronavirus - in a fundamentally different branch - on the left, 2s. It can be seen that the latter are very far evolutionary from the current coronavirus.

Four types of coronaviruses have long been known as human pathogens that cause respiratory infections and have a kinship with viruses of bats, but did not switch to a person directly from them. This transition process began not twenty or fifty years ago, but maybe several hundred or even thousands of years ago, and this process does not stop. At the same time, coronaviruses switched to a person not directly from bats, but through some intermediate host. Such intermediate masters could be, for example, cows, pigs, goats, sheep or some other animals that are much more close to a person than a bat. We now have data about all three coronaviruses that have arisen over the past 20 years and which have struck a person: these are, for example, torso-coronaviruses that came from the bats virus, intermediate passages on palm c noty and after that spread to a person. And the virus of the Middle Eastern respiratory syndrome came from the coronavirus of Egyptian bats and, as already mentioned, reached a person through camels. These bats managed to cultivate in captivity, and now they serve virus -men with a model for the study of coronaviruses. The current coronavirus also came from bats, but from a completely different variety. Perhaps its intermediate masters were either Pangolins or some kind of pets-most likely a dog or cat. Which, I think, will become clear over the next two to three months. There are already suspicions.

Sergey Nusovov , Dokt. Biol. sciences, professor, member-corr. RAS,
Head. Laboratory of biotechnology and virology of the Faculty of Natural Sciences
Novosibirsk State University

Lecture decoding:
Maria Molina

1. YouTube.com/watch?v=zrchaisbu6q
2. Organization of the Alpha Coronavirus genome: Fields Virology. 6th ed. Wolters Kluwer, Lippincott-Williams & Wilkins. Philadelphia - New York. 2013.
3. The dynamics of incidence: gisanddata.maps.arcgis.com