The Atlantic (USA): hope for a cure for coronavirus | Science | Foreign media

Twenty nine. This is the maximum amount of protein in the arsenal of the new coronavirus to attack human cells. That is, 29 proteins against tens of thousands of proteins that make up the much more complex and finely organized human body. 29 proteins that have captured a sufficient number of cells in a sufficient number of organisms to kill more than 80,000 people and put the whole world on a joke.

If it becomes possible to stop COVID-19 (using a vaccine, treatment, drug), then this will be done by blocking such proteins so that they cannot capture, suppress and bypass the human cellular mechanism. Coronavirus, with its pathetic 29 proteins, may seem like a primitive trifle, but it is because of this that it is so difficult to fight with it. He has very few weaknesses to take advantage of. For comparison: bacteria can contain hundreds of proteins.

Scientists are struggling to find the vulnerabilities of the SARS-CoV-2 coronavirus, which causes COVID-19, having been searching since it was discovered that it was he who caused the mysterious cases of pneumonia in January in Wuhan, China. In three short months, laboratories from around the world were able to target individual proteins, computing and drawing some of their structures atom by atom with record speed. Other researchers are studying molecular libraries and the blood of those who have recovered in search of substances that can firmly bind and suppress these viral proteins. Now more than 100 approved and experimental drugs are being tested for possible use against COVID-19. In mid-March, the first volunteer was given an experimental vaccine from Modern.

And some researchers test how these 29 proteins interact with different parts of the human cell. The purpose of research is to find drugs that attack the host, but not the virus. This seems like something far from the fight against the virus, but such searches allow you to monitor the cycle of virus replication. Unlike bacteria, viruses cannot copy themselves. “The virus uses host mechanisms,” says microbiologist Adolfo García-Sastre, who works at the Icana School of Medicine at Mount Sinai Medical Center. They trick the host cells into copying their viral genomes and making their viral proteins.” class=”article-body__related-article-image” rel=”noopener noreferrer”>” rel=”publisher noopener noreferrer”>CNBC

04/12/2020” rel=”publisher noopener noreferrer”>The conversion


One idea is to stop such work, which was started by order of the virus, without interfering with the normal functioning of the cell. Here it is hardly possible to draw an analogy with an antibiotic to combat SARS-CoV-2, which kills foreign bacterial cells indiscriminately. “I think it’s more like cancer therapy,” Kevan Shokat, a pharmacologist at the University of California at San Francisco, told me. In other words, we can talk about the selective destruction of human cells that were peddling. This makes it possible to deal with additional targets, but there is also a problem. The drug is much easier to recognize the difference between a person and a bacterium than between a person and a person who has undergone a virus attack.

Thus, antiviral drugs rarely become a “miracle cure,” like antibiotics against bacteria. The drug Tamiflu, for example, can reduce the duration of acute respiratory viral infections by a day or two, but it is not able to completely cure the disease. HIV and hepatitis C drugs must be taken in a mixture with two or three other drugs, because the virus can mutate quickly and become resistant. The good news about SARS-CoV-2 is that it doesn’t mutate very quickly by viral standards. In the process of the disease, you can choose other goals for treatment.

Prevent the virus from entering the cell

Let’s start with where the virus appears. The virus trickles into the host cell. SARS-CoV-2 is coated with spiked protein, similar to lollipop. The tips of these spikes can attach to the ACE2 receptor, which is present in some human cells. It is because of these spiky proteins that the coronaviruses from the group including SARS-CoV-2, MERS-CoV (Middle East Respiratory Syndrome Coronavirus) and SARS (SARS virus) got their name – because they create a kind of corona. These three coronaviruses are so similar because of their spike proteins that scientists use a treatment strategy for MERS and SARS to fight SARS-CoV-2. Clinical trials of the vaccine from Modern have been able to start so quickly because they are based on previous studies of the MERS protein.

Spiky protein is also the focus of antibody treatment. Such methods of treatment can be developed faster than creating a new pill, because in this case the strength of the human immune system is activated. The immune system causes protein compounds called antibodies to neutralize foreign proteins such as those introduced by the virus. Some US hospitals are attempting to transfuse patients with antibody-rich blood plasma from those who have successfully had COVID-19. Currently, research teams and biotechnological companies are also testing the plasma of the recovered with the aim of determining antibodies that can be produced in large quantities in factories. Spiky protein is a logical target for antibodies, because there is a lot of it outside the virus. Again, the similarities between SARS-CoV-2 and SARS are beneficial here. “It is so similar to SARS that we got a head start and made a breakthrough at the start,” says program manager Amy Jenkins of the Department of Defense’s Advanced Research Projects Office, which funds four different teams working on antibody therapy for the treatment of COVID-19.” class=”article-body__related-article-image” rel=”noopener noreferrer”>New York during emergency mode” rel=”publisher noopener noreferrer”>The Atlantic

04/03/2020” rel=”publisher noopener noreferrer”>Nature


But the SARS-CoV-2 virus is not enough to just attach its spike protein to the receptor to get inside the cell. In fact, the spike protein is passive until it is split in two. The virus uses another human enzyme, say, furin or TMPRSS2 (an inconsistent name), which involuntarily activates a spike protein. Some experimental drugs are designed to prevent these enzymes from unintentionally carrying out the work of the virus. One of the possible mechanisms that caused the big hype medication for malaria, hydroxychloroquine, on which Trump was stuck, just consists in suppressing the activity of thorns.

When the spike protein is activated, SARS-CoV-2 fuses with the membrane of the host cell. He injects his genome and penetrates inside.

Prevent virus reproduction

In a human cell, the naked SARS-CoV-2 genome seems to be a specific type of RNA, a molecule that usually gives directions for creating new proteins. Therefore, a human cell, likened to a soldier who received a new order, dutifully begins to produce new viral proteins, and new viruses appear.

Replication is a rather complex process that antiviral drugs can act on. “There are many, many proteins involved … and many potential targets,” said virologist Melanie Ott, who works at the Gladstone Research Institute and the University of California, San Francisco. For example, the experimental antiviral drug Remdesivir, which is undergoing clinical trials for suitability for the treatment of COVID-19, acts on a viral protein that copies RNA, and then the process of copying the genome is disrupted. Other viral protease proteins are necessary for the release of viral proteins that are linked into one long strand so that they can detach and help the virus reproduce itself. And some proteins help to modify the inner membrane of a human cell, creating bubbles there that turn into small viral factories. “The replication mechanism sits on the envelope, and then suddenly begins to produce tons of viral RNA, doing it again and again,” Matthew Frieman, a virologist at the University of Maryland’s School of Medicine, told me.

In addition to the proteins that help the virus replicate itself, and to the spiky proteins that make up the outer capsule of the coronavirus, SARS-CoV-2 has a set of very mysterious accessory proteins that are unique and unique to this virus. According to Freeman, if you understand what these accessory proteins are for, scientists will be able to discover other ways of interacting SARS-CoV-2 with a human cell. It is possible that accessory proteins help the virus somehow bypass the natural antiviral defense of human cells. In this case, this is another potential target for the drug. “If you interrupt this process,” Freeman said, “you can help the cell suppress the virus.”” class=”article-body__related-article-image” rel=”noopener noreferrer”>New York Central Park Field Hospital” rel=”publisher noopener noreferrer”>CNBC

04/12/2020” rel=”publisher noopener noreferrer”>The conversion


So that the immune system does not fail

Most likely, antiviral drugs are most effective in the early stages of infection, when the virus has infected a few cells and made few copies of itself. “If you give antiviral drugs too late, the risk is that the immune component is already broken by now,” Ott says. In the specific case of COVID-19, those patients who become ill seriously and incurably experience the so-called cytokine storm, when the disease causes a violent and uncontrolled immune response. This is unnatural, but a cytokine storm can even affect the lungs, sometimes very seriously, because it accumulates fluid in the tissues. This is explained by the immunologist from the Children’s Research Hospital of St. Jude Stephen Gottschalk (Stephen Gottschalk). Thus, another way to combat COVID-19 is to influence the immune response, not the virus itself.

A cytokine storm does not only occur during COVID-19 and other infectious diseases. It is possible in patients with hereditary diseases, with autoimmune diseases, in those who have had bone marrow transplantation. Those drugs that soothe the immune system in these patients are now reprofiling to combat COVID-19 by conducting clinical trials. Rheumatologist from the University of Alabama, Randy Cron, plans to conduct small trials of the immunosuppressant Anakinra, which is currently used in the treatment of rheumatoid arthritis. Other commercially available drugs, such as tocilizumab and ruxolitinib, which were developed, respectively, for the treatment of arthritis and bone marrow, are being reprofiled. Fighting a viral infection by suppressing the immune system is quite problematic, because the patient must be rid of the virus at the same time.

Moreover, Crohn says, COVID-19’s disease statistics indicate that the cytokine storm during this disease is unique, even when compared to other respiratory infections like the flu. “It starts very quickly in the lungs,” says Cron. But at the same time, it affects other organs less. The biomarkers of such a cytokine storm are not as “terribly” high as usual, although the lungs are very affected. In the end, COVID-19 and the virus causing this disease are unknown to science.

Initial studies to create drugs against COVID-19 focused on re-profiling existing drugs, because this way a patient lying on a hospital bed can get at least something faster. Doctors already know their side effects, and companies know how to produce them. But these redesigned drugs are unlikely to be a panacea for COVID-19, unless researchers are incredibly lucky. However, these drugs can help a patient with a mild form of the disease, preventing him from developing into a severe form. And this will release one ventilator. “Over time, we will certainly achieve great success, but for now, we need something to get started,” says Garcia-Sastre.

InoSMI materials contain estimates of exclusively foreign media and do not reflect the position of the InoSMI editorial staff.

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