Albert Rizvanov on COVID-2019: “An unfortunate combination for humanity has fallen”

The director of the scientific and clinical centre for precision and regenerative medicine at the Kazan Federal University (KFU) about the development of anti-coronavirus vaccine and his forecast of developments

Albert Rizvanov on COVID-2019: “An unfortunate combination for humanity has fallen”
Photo: Maksim Platonov

In early March, the KFU launched a project to develop a gene-therapeutic version of a vaccine against the new type of coronavirus. Its creation will cost about 5 million rubles. Then it will require major investment and assistance from partners working with a “live” infectious virus in conducting tests. Albert Rizvanov, the director of clinical research centre of precision and regenerative medicine of the KFU, Doctor of Biology, head of the work on a vaccine in Kazan, told Realnoe Vremya about when it will be synthesized and tested in animals and humans, why big pharmaceutical companies don't want to actively participate in vaccine production, whether the virus will weaken with the coming of warm weather, what pandemic teaches the world community, and much more.

“Four major coronaviruses constantly circulate in human population”

Is it true that currently there are more than 40 coronaviruses described in the world?

Yes, it is. Four major coronaviruses constantly circulate in human population. Some of them cause respiratory diseases, some — intestinal disorders. Even in seasonal outbreaks, when people get ARVI, from 10 to 30 percent are coronavirus infections, only these are not Chinese, but ordinary coronaviruses.

Why, if more than 40 coronaviruses have been detected, has COVID-2019 turned the whole world upside down?

There has appeared a plus one coronavirus. And this happened as a result of natural processes in nature. Viruses in nature constantly change, genetic information is exchanged between different strains, and new genetic variants appear. Most of these variants differ little in terms of infectivity from their parent strains.

But in this case, unfortunately, it's been an unfortunate combination for humanity. As a result, the virus is not only transmitted from animal to human but also has the ability to be effectively transmitted from person to person. For example, mouse plague (hemorrhagic fever with renal syndrome caused by hantaviruses) is transmitted to humans only from a rodent. Moreover, the new version of the coronavirus is transmitted better than the flu virus, meaning the Chinese coronavirus is more infectious. Although COVID-2019 is not a record holder in this sense, measles, for example, is much more contagious.

Why is it that COVID-2019 can live on surfaces for such a long time?

This is a fairly typical time of life outside the body. There are viruses that are much more resistant. Fortunately, COVID-2019 is not the most resistant, there are viruses whose shell is completely protein, more stable. The current coronavirus's shell contains lipid layers — in fact, it is covered with a membrane, like a very small soap bubble, its shell is not so resistant. But, really, depending on the type of surface, the new coronavirus can be in the environment outside of the human body for several hours to several days.

Moreover, the new version of the coronavirus is transmitted better than the flu virus, meaning the Chinese coronavirus is more infectious. Although COVID-2019 is not a record holder in this sense, measles, for example, is much more contagious

“It usually takes a virus centuries to adapt to its host”

Recently, there has been news that a man was identified in Iceland who was infected with two strains of COVID-2019 at once. As I understand it, the “task” of any virus is not to kill a person, but to infect as many people as possible and spread effectively. So, the idea is that after the mutations it is expected to become less aggressive?

In fact, this evolutionary process of the virus can take a very long time. Adaptation to the host takes much longer than a single epidemic. This usually takes centuries. Evolutionarily ancient viruses are adapted to coexist with the body, causing it minimal inconvenience. And “young” viruses that have recently entered the host's body usually cause more severe diseases.

About the case of infection with two strains... in principle, this happens in nature. Plus, it happens that the virus mutates inside the body and is not in the form of a single strain, but in the form of several genetic variants. In this case, additional research is needed. Once is not a statistic. We can assume anything from errors in diagnosis to a variety of options — that the mutation occurred directly in the host or there was an infection with two strains at once.

In essence, COVID-2019 also appeared as a result of one organism (most likely one of the wild animals on the market in Hubei) being infected with two strains of the virus — bat coronavirus and another animal. And between these coronaviruses, there was a genetic recombination, an exchange of genetic information, as a result of which a new genetic variant of the coronavirus was born.

The virus cannot live outside the host cell. In fact, it is an intracellular parasite. But whether he is alive or not is a philosophical concept. Viruses can actually reproduce themselves. And this is part of the living. But they can't live without another life

“The virus is like Schrodinger's Cat, both alive and dead”

The order of the Moscow Department of Healthcare states that a patient diagnosed with the new coronavirus infection who is at home should take lopinavir and ritonavir, which are used in HIV therapy, in the early stage of the disease. Is there a link between COVID-2019 and HIV?

There is no evidence that this drug is effective for treating the current coronavirus infection. It's just that HIV is also an RNA-containing virus. There is an assumption that if you use drugs that act on viral RNA polymerase, it may be possible to suppress the new coronavirus. But for now, this is just an assumption.

Abroad, a combination of two drugs is recommended, but there we are talking about a drug for malaria (hydroxychloroquine) and an antibiotic. So far, there is no drug that would act on COVID-2019 itself. All treatment is purely symptomatic. And this American combination of drugs against malaria plus an antibiotic is aimed at reducing the inflammatory response in the lungs. Due to inflammatory processes, pathogenic microflora grows, which causes lung inflammation and sepsis. And these drugs do not act on the virus itself, but only reduce inflammatory processes, have an immunomodulatory effect, which allows the body to fight the virus. But this is not a specific therapy.

If we talk about the nature of the virus, in your opinion, is the virus a living, dead or some kind of transitional state?

The virus cannot live outside the host cell. In fact, it is an intracellular parasite. But whether he is alive or not is a philosophical concept. Viruses can actually reproduce themselves. And this is part of the living. But they can't live without another life. The virus is like Schrodinger's Cat, both alive and dead. But in essence, the virus is more alive than dead. On the surface, the virus does not live, does not multiply, but simply exists, it just freezes in time, at this time, there are no biochemical processes in it. But if the virus is transferred to another planet, the spark of life will not be generated there.

We synthesize a DNA vaccine based on genetic engineering. The synthesis process is currently underway. In a month and a half, we will have, relatively speaking, a test tube with this vaccine, and we will start testing it on cells and laboratory animals

“In a month and a half, we will have, relatively speaking, a test tube with a vaccine”

In March, scientists at the Kazan Federal University have begun to develop a vaccine against the virus. As far as I know, you are working with a published genome, not a live vaccine. What is the special feature of your development?

We are synthesising a DNA vaccine based on genetic engineering. The synthesis process is currently underway. In a month and a half, we will have, relatively speaking, a test tube with this vaccine, and we will start testing it on cells and laboratory animals.

I'll give you an analogy to make it clearer. For 3D printers, you don't have to have the part itself on hand to create it — it is enough to have just digital drawings. For living organisms, the genome is such digital drawing. Chinese scientists decoded the genome of the coronavirus in December and published it in the public domain. We took this information and identified areas that encode different viral proteins. As a result, we should get a DNA vaccine, or a gene vaccine. That is, it will be a piece of DNA containing individual viral genes that encode individual viral proteins. This does not require the presence of the virus itself or other infectious material, which we do not have. If a gene drug is introduced into a cell, the cell must read this genetic information and begin to synthesize viral proteins. The body's immune system recognizes them as foreign, and a protective reaction is developed in the form of antibodies and T cells that kill the virus and infected cells. Thus, our DNA vaccine will lead to the development of immunity against a new coronavirus infection.

If the experiments with animals are successful, how long will it take to launch industrial production of the vaccine?

It will take several more months for official preclinical studies to be conducted on animals, with already living virus. After that, human experiments will be started. It is difficult for me to estimate the duration because it depends on several factors — funding, availability of partners who have permission to work with infectious material. Creating the prototype of the vaccine itself is a fairly quick process that will take about three months. The testing process takes much more time and resources.

The first stage, the development of a prototype of the vaccine, in the KFU is funded by DNA Research Centre ANO. Just a few days ago, the ministry of science and higher education of the Russian Federation requested information on subordinate organizations about who is developing vaccines and testing systems for COVID-2019. The Kazan Federal University also provided this information to the ministry. We may be part of some government programme to support research on the new coronavirus.

My American doctoral dissertation was devoted to the creation of gene-therapeutic vaccines and the diversity of hantaviruses in nature. We can say that the experience gained in the US allowed me to apply it to the development of current drug candidates

What do you think the new coronavirus pandemic should teach the world community?

The development of medicines and vaccines is now highly regulated. This, of course, is done in order to protect people, so that medicines are fully tested for effectiveness and safety. But classic schemes imply that many years pass before a drug appears on the market.

This system may be justified for conventional medicines, but it is not fast enough for vaccines in extreme situations. This requires the modernization of the legal framework plus the development of new technologies. Including the use of genetic engineering. All this would reduce the cycle of production and development of new vaccines.

How much can your technology shorten the development cycle?

Potentially — several times. We can develop a prototype of the vaccine in two months. But even when you develop a vaccine, you need to test it to make sure it's safe. This, unfortunately, takes a long time. Here every time you need to weigh all the pros and cons. There are no absolutely safe medications. Even clean water can kill you if you drink a lot of it, and some people are even allergic to water.

Another lesson is the rapid development of test systems should be en masse, so that the state has a tool for rapid diagnosis and isolation of people who have become carriers of the virus at the first cases of a threat. It also requires the acceleration of procedures of registration and production. Under current legislation, it is impossible to deploy genetic testing, for example, at an airport.

By Kristina Ivanova. Photo: Maksim Platonov
Tatarstan