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Apr 27, 2021
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Coronavirus mutations in light of the third wave of the COVID-19 pandemic

As of the date of this writing – April 19, 2021, the total number of people infected with the SARS-CoV-2 virus in the world is more than 142 million people, the death toll is more than 3 million.Thus, the number of cases of infection in the last 2 weeks – from 06.04 .21 to 19.04.21 increased by 10 million people. [1]… In Russia, on the same date, the total number of cases is more than 4.5 million people, the deaths – more than 105 thousand people [2]…

The most leading in the number of deaths from COVID-19 (indicator per 100 thousand population): Great Britain – 201.8; Italy – 192.7; Brazil – 181.8; USA – 175.0; Spain – 165.8; France – 151.2;. For Russia, this figure is 70.7 per 100 thousand people (data from 18.04.21). An important coefficient of the spread of the virus is the Rt indicator – as the ratio of the number of newly detected cases of infection in the last 4 days to the number of new cases in the previous 4 days. A value of> 1 indicates a worsening epidemiological situation and a greater spread of infection. In India, Brazil, Turkey, Italy, the Rt indicator, according to data from 04/18/21, exceeds the value of 1. In Russia, this indicator is 1.07, in the USA – 0.92 [3]…

The given information convincingly testifies to the 3rd wave of the pandemic, which was officially recorded in many countries of the world. These circumstances are associated with the formation and widespread distribution of strains of the SARS-CoV-2 coronavirus that have undergone genetic mutations.

Mutation is a molecular biological process when, in the process of viral replication, “knocks” occur at the stages of transcription and translation, i.e. during the “rewriting” of the genetic code from the RNA of the virus to the DNA of the host cell. Such errors in DNA lead to the formation of altered genes encoding the proteins of the virus, as a result of which such new mutant viruses appear, with altered properties of their own proteins.

Major mutations of the coronavirus occur in the gene for the glycoprotein S-protein (D614G), RBD-domain (N501Y) and furin cleavage site (P681H). Thus, a mutation in the S protein leads to the replacement of the aspartic amino acid (abbreviated as D) with the amino acid glycine (abbreviated as G). American researchers have experimentally shown that the long-discussed D614G mutation in the S-protein gene of the SARS-CoV-2 coronavirus increases its infectivity, so this variant of the virus spreads faster. A viral protein with this mutation is also more stable. Mutations in the RBD-receptor binding domain have a higher affinity for the receptor for angiotensin converting enzyme type 2 (ACE2) of human epithelial cells, which allows the coronavirus to penetrate them more confidently.

The main mutational lines of the SARS-CoV-2 virus:

one. “British” strain coronavirus. Name: B.1.1.7. The most important mutations it contains are: – N501Y (this mutation makes the virus more infectious), 70del-69 and P681H. The WHO reported that the “British” strain of the coronavirus has been identified in at least 60 countries.

2. “South African” strain coronavirus. Names: B.1.351 and 501Y. V2. The most important mutations it contains: N501Y, K417H, E484K. The last mutation is considered the most dangerous mutation – viruses with the E484K mutation are able to more effectively evade antibodies obtained from the blood plasma of patients who have recovered from COVID-19. Scientists warned that the strain found in South Africa transmits about 50% faster and overcomes some of the antibodies produced in response to other variants of the virus.

3. “Brazilian” strain coronavirus. Name: B.1.1.248

The most important mutations it contains are N501Y, E484K.

The “Brazilian” strain is the most contagious to date. It is resistant to immunity acquired after the first wave of coronavirus.

So, the main mutation of the coronavirus is N501Y, it is contained in the gene encoding the S-protein synthesis (“thorn”, Spike). This mutation is also typical for two other strains – “South African” and “Brazilian”. This mutation changes the shape of the “spike” (S-protein), with which it more efficiently attaches to the ACE2 receptor. According to the authors, the “British” strain with this mutation is 50-70% more infectious than the classic SARS-CoV-2 virus.

4. It should be noted that the most dominant in Europe has become the so-called. The “Spanish strain” of the coronavirus is the 20A.EU1 line, a major mutation in the S-protein called A222V. Immunoglobulins are less effective at neutralizing “Spanish” strain coronavirus.

five. “California” strain. Discovered in the USA – name CAL.20C, main mutations: S13I, W152C and L452R.

6. “Romanian” strain – a kind of “British” – resistant to vaccines (line B.1.1.7 + E484K, main mutations: E484K).

7. Siberian and Northwest strain coronavirus. These are newly formed new mutations on the territory of Russia. While there is little data on these strains, it is known that mutations also occur in the region of the gene responsible for the S-protein.

According to Rospetrebnadzor, as of April 16, 2021, 192 samples of the British strain, 21 of the South African strain were identified in the Russian Federation. [6-9]…

Researchers in the UK reported that the risk of death in people infected with the “British” strain B.1.1.7 is higher than in those infected with other strains, on average 64%. The absolute risk of death rises from 2.5 to 4.1 deaths per 1000 infections [10]…

Scientists from Cape Town and Johannesburg (South Africa) studied antibodies in 89 people hospitalized with COVID-19 in early 2021. The authors showed that COVID-19, carried during the first wave, does not provide protection against some of the new variants of the virus. However, people infected with the “South African” strain of SARS-CoV-2 have neutralizing antibodies against older variants of the virus, as well as against the “Brazilian” strain.

Scientists from the United States studied a cohort of pregnant and lactating mothers who received the Pfizer / BioNTech or Moderna vaccine. They showed that the levels of IgG, IgA and IgM to the S-protein and receptor-binding domain (RBD) increased in the blood of women from both groups. Antibodies, especially IgG, were passed to the baby through the placenta and breast milk. The authors showed that maternal IgG can cross the placental barrier. IgG to the S-protein and RBD-domain were detected in all ten cord blood samples. The level of antibodies to SARS-CoV-2 was significantly higher in vaccinated women than in those with COVID-19, and the concentration of IgG in the mother’s blood increased after the second dose of vaccine [12]…

This fact testifies in favor of vaccinating this contingent.

Japanese scientists, in particular Yoriyuki Konno et al., In the work of 20 years, showed that the protein expressed from the ORF3b gene of the new coronavirus SARS-CoV-2 strongly suppresses the synthesis of type I interferons in patients with COVID-19. / At the same time, the virus is sensitive to interferons, which speaks of their potential effectiveness for the treatment of coronavirus infection [13]…

In this regard, in clinical terms, it seems advisable to provide patients with the appointment of recombinant interferon-α2b preparations with antioxidants as measures of active antiviral protection, both in the pre-vaccine period, when the formation of neutralizing antibodies is underway, and in the late post-vaccination period, when the antibody titer after vaccination starts to decline. An example of such a complex interferon-containing drug is the domestic drug Viferon.

Bibliography:

1.https: //coronavirus-monitor.ru/;

2.https: //stopcoronavirus.rf/;

3.https: //stopcoronavirus.rf/;

4. Zhang l., Et al. // The D614G mutation in the SARS-CoV-2 spike protein decreases S1 secretion and increases infectivity. // Preprint bioRxiv, 2020, DOI: 10.1101 / 2020.06.12.148726;

5. Wrapp, D. Wang N., Corbett KS, Goldsmith JA et al. Cryo-EM structure of the 2019-nCoV peak in pre-fusion conformation // Science 13 Mar 2020: Vol. 367, Issue 6483, pp. 1260-1263;

6. Zhang W., et al. // Emergence of a new variant of SARS-CoV-2 in Southern California // JAMA. published on the website on February 11, 2021, DOI: 10.1001 / jama.2021.1612;

7. Valensky R.P., Walk H.T., Fauci A.S., SARS-CoV-2. US Options of Concern – Challenges and Opportunities // JAMA. 2021; 325 (11): 1037-1038. DOI: 10.1001 / jama.2021.2294;

8.https://spid.center/ru/articles/2937;

9.https: //www.kommersant.ru/doc/4781182?utm_source=yxnews&utm_medium=desktop;

10. Challen R., et al. // Risk of mortality in patients infected with a dangerous variant of SARS-CoV-2 202012/1: an agreed cohort study // BMJ 2021; 372: n579, published March 10, 2021, DOI: 10.1136 / bmj.n579;

11. Tandeka Moyo-Gwete et al. // SARS-CoV-2 501Y.V2 (B.1.351) causes cross-reactive neutralizing antibodies. // bioRxiv, 2021, DOI: 10.1101 / 2021.03.06.434193v2;

12. Gray C.J. et al. // COVID-19 vaccine response in pregnant and lactating women: a cohort study // AJOG, published March 25, 2021, DOI: 10.1016 / j.ajog.2021.03.023;

13. Konno Y. et al. SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further enhanced by a naturally occurring extension variant. // bioRxiv, May 12, 2020; DOI: 10.1101 / 2020.05.11.088179.


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