Researchers from Sechenov University together with Russian and Iranian colleagues described currently known approaches to the treatment of SARS-CoV-2 infection. In the paper published in Journal of Molecular Medicine, they wrote about how different groups of drugs worked and how promising each approach was.
SARS-CoV-2 — a coronavirus that caused the pandemic in early 2020 — is a close relative of two other viruses (SARS-CoV and MERS-CoV) that triggered epidemics in 2003 and 2013-2015. Most often, the disease is accompanied by fever, dry cough, increased fatigue, and loss of taste and smell. Most symptoms are associated with an overreaction of the patient’s immune system, which, in severe cases, causes damage to lung tissue and systemic inflammation.
The first approach considered in the article is immunotherapy. It is known that antibodies contained in the serum of people who have had a viral disease can speed up the recovery of other patients. Despite the simplicity of this method, it has several limitations: the number of potential donors is still small, the activity of antibodies decreases over time (which is why the serum from the patients who had the disease long ago is less valuable), and the antibodies themselves can help the virus spread in the body — a phenomenon known as antibody-dependent enhancement of infection.
Similarly, we can use T-lymphocytes — cells that can destroy damaged or infected cells of the body. Scientists have noticed that the number of T-cells of the CD8+ subpopulation is significantly reduced in patients with COVID-19, and the more severe the disease the lower this number. T-cells directed against a specific virus can be produced in vitro and offered to patients as therapy.
Another area of research is related to the suppression of certain enzymes, in particular AAK1 and GAK, which are needed for the virus to enter a cell. Some of the drugs that act as inhibitors of these enzymes have already been tested and used, although for another purpose, such as, for example, the treatment of rheumatoid arthritis (this approach is called ‘drug repurposing’).
‘Analysis of clinical trials registered in ClinicalTrials.gov has shown a wide variety of therapeutic agents offered for the treatment of COVID-19. And, of course, most of them are associated with the use of previously known drugs used in the treatment of other diseases,’ commented Anastasia Shpichka, one of the authors of the study, a leading researcher at the Institute for Regenerative Medicine, Sechenov University.
There are other ways to prevent the virus from entering cells. Since the receptor that is built into the cell membrane and lets the virus inside is known (this is the ACE2 protein), it is possible to create an analogue that will bind to viral particles and ‘distract’ them from the patient’s cells. Such analogues of the ACE2 receptor have already been developed, tested and shown to slow down the spread of the virus in the body, but not stop it, which indicates the presence of other entry points into human cells.
The use of antiviral drugs gives contradictory results. Remdesivir, which showed good efficacy against SARS-CoV-2 in some studies, did not bring noticeable benefits in others. Chloroquine, used to treat malaria, was considered a promising drug, but its side effects do not allow it to be recommended for the treatment of COVID-19. Attempts to use HIV medications against SARS-CoV-2 also yield mixed results.
One more direction in the fight against COVID-19 is suppression of excessive immune system reaction, which especially affects the lung tissue. One treatment option may be mesenchymal stem cells, used in the treatment of inflammatory and autoimmune diseases. Studies of the effectiveness of this method in the treatment of COVID-19 are already underway. Another class of drugs that limit inflammatory response is corticosteroids. They can reduce mortality among patients with severe disease.
Despite the efforts of scientists from all over the world, aimed at finding an effective COVID-19 treatment, the optimal algorithm has not yet been found. The key to creating a drug can be either a discovery as part of one of these approaches or a new solution, for example, found at the intersection of scientific disciplines or borrowed from the experience of treating other diseases.
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