A study on the SARS-CoV-2 B.1.620 line

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly mutating. To date, several different different SARS-CoV-2 lines have emerged in several geographic areas around the world.

In a recently published Nature communication In a study, the authors describe the B.1.620 line discovered in Lithuania. According to this study, the lineage is said to have originated in the Central African Republic and then spread to several neighboring countries across Europe as well as the United States.

To learn: Origin and distribution of the SARS-CoV-2 line B.1.620 with a variant of worrying mutations and deletions. Image source: Fit Ztudio / Shutterstock.com

GISAID

The Global Initiative on Sharing Avian Influenza Data (GISAID) aims to integrate the efforts of the international scientific community to understand the spread and evolution of influenza viruses. As a result of this initiative, scientists have full access to comprehensive genetic sequencing, clinical and epidemiological data on virus isolates.

GISAID is a community resource project that was originally founded in 2008. Since the start of the 2019 coronavirus disease (COVID-19) pandemic, GISAID has proven to be a valuable resource for disseminating SARS-CoV-2 genome data and for inferring the emergence and dissemination of multiple SARS-CoV-2 lines.

The B.1.620 line

B.1.620, which was first identified in Lithuania, has the spike protein mutation E484K. Due to repeated reports of this mutation, this lineage was redirected to sequencing.

A search for relatives of this line on GISAID initially showed some genomes from Europe; however, other relatives of this tribe are still being found. B.1.620 has a Pango line designation that is integrated into GISAID.

This line now includes genomes from France, Switzerland, Belgium, Germany, England, Scotland, Italy, Spain, Czech Republic, Norway, Sweden, Ireland, Portugal, the United States, Canada and most recently the Philippines and South Korea. First European cases of B.1.620 concerned travelers returning from Cameroon; more recently, however, genomes from the Central African Republic, Equatorial Guinea, the Democratic Republic of the Congo, Gabon and the Republic of the Congo have also been submitted to GISAID.

VOC mutations and deletions within the B.1.620 line

B. 1,620 genomes carry a large number of unique mutations. In fact, this SARS-CoV-2 strain is 18 mutations away from closest relatives and 26 from the reference strain Wuhan-Hu-1.

B.1.620 shares multiple mutations and deletions with known SARS-CoV-2 Variants of Concern (VOCs), including HV69 / 70Δ, LLA241 / 243Δ, S477N, E484K, and P681H. However, it does not appear to be of recombinant origin.

The scientists in the current study determined exact travel dates and travel history using GISAID-related metadata and by contacting the submitting laboratories who contacted the patient’s home laboratory or family doctor.

Based on travel-related cases of B.1.620, the scientists suspected Cameroon as the direct source of this lineage. The genomes of GISAID from Cameroon were diverse and revealing, suggesting that they may be distant relatives of B.1.620.

During this study, SARS-CoV-2 genomes from the Central African Republic were deposited on GISAID; however, none of them resembled the ancestors or sibling lines of B.1.620.

B.1.620 can escape antibody-mediated immunity

B.1.620 carries the D614G mutation, which increases the infectivity of SARS-CoV-2 due to its increased interactions with the angiotensin converting enzyme 2 receptor (ACE-2). B.1.620 also carries the mutations P26S, HV69 / 70Δ, V126A, Y144Δ, LLA241 / 243Δ and H245Y in the N-terminal domain (NTD) of the spike protein. These mutations may have arisen as an escape from antibody-mediated immunity.

The spike protein from B.1.620 also carries S477N and E484K mutations in the receptor binding domain (RBD) of the spike protein. In contrast to other VOCs, however, this SARS-CoV-2 strain does not carry the mutations N501Y or K417.

Using in silico the scientists modeled the RBD-ACE-2 interface with the substitutions S477N and E484K. Molecular dynamic simulation of this interface showed that B.1.620 can escape antibody-mediated immunity while maintaining a beneficial interaction with the ACE-2 receptor.

B. 1,620 in Lithuania and Europe

In Lithuania, strain B.1.620 was found 2.4 times more often in vaccine breakthroughs compared to its population prevalence. The frequency of B.1.620 appeared relatively stable, albeit at a low level, in the five most affected European countries, Lithuania, Germany, Switzerland, France and Belgium. This can be attributed to increasing vaccination rates and improving weather in Europe.

There is a sustained widespread outbreak of B.1.620 in Lithuania. However, genomes of this lineage have been found from other regions in Europe. These other B.1.620 genomes from Europe appear to indicate ongoing transmission in Europe.

B. 1,620 in Central Africa

The scientists compiled the genome dataset B.1.620. They had seven genomes from travelers, six of which were taken in the Central African Republic (CAR) near the Cameroon border. This indicates that Central Africa is the most plausible geographic region where B.1.620 is widespread.

The individual travel stories that the scientists have collected indicate several independent introductions of B.1.620 in Europe. There have been documented cases of infected travelers returning from Cameroon to Belgium, France and Switzerland, and from Mali to the Czech Republic.

The scientists find evidence of persistent local transmission of B.1.620 within Belgium.

Using a Bayesian phylogeographic inference method, the scientists deduce an African origin of the line B.1.620.

After this study, the variant then spread through multiple introductions in various European countries. Subsequent phylogeographic analyzes at the country level indicated Central Africa as the likely origin of this lineage.

This study suggests that B.1.620 may be more prevalent in Africa and that its detection in Europe was mainly in countries with current active genome surveillance programs. Detection of B.1.620 in African neighbors of Cameroon and the Central African Republic such as Equatorial Guinea, Gabon and the Democratic Republic of the Congo, even at low sequencing levels, suggests that B.1.620 may be common in Central Africa.

effects

The current study highlights the global inequalities in the surveillance of infectious diseases. These inequalities affect the world as it is a global pandemic. In addition, the results discussed here underscore the importance of collecting and sharing related metadata with genome sequences such as travel stories.

Overall, the scientific community should not undermine the importance of the consistent and standardized exchange of critical metadata.


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