#15,819
Overnight Japan announced the discovery of 91 infections in the Kanto region (which includes the Greater Tokyo Area) of a new COVID variant which carries the problematic E484K mutation. This is the same mutation that has cropped up in the South African (B1.351) and Brazilian (P.1) variants, that is feared may negatively impact vaccine effectiveness and evade previous immunity.
This new variant differs from B.1.351 and P.1 in that it doesn't appear to carry the 501Y mutation, which has been linked to increased transmissibility of the virus. For now this is being classified as a B.1.1.316 lineage with the E484K mutation, but without N501Y.
Whether this new variant can successfully compete against the host of other emerging COVID variants is uncertain, but 91 cases reported in the Kanto region is a matter of some concern. Today Japan's National Institute of Infectious Diseases (NIID) published the following (translated) technical report on what is known at this time.
(Breaking news publication date 2021/2/19)
Spike protein E484K mutation in the new coronavirus mutant strain
In order to support the active epidemiological investigation of local governments, the genome sequence of SARS-CoV-2 (single-strand plus RNA virus, total length 29.9 kb) was determined and sequenced in GISAID * 1, and genes specific to infected clusters. Information and commonality between clusters are being analyzed. So far, four interim reports have outlined the status of domestic transmission (April 27, 2020 1) , August 6, 2020 2) , December 11, 2020 3) , January 14, 2021. Day 4) ). Although the influx of the European system (Pangolin * 2 system B.1.1.114) was observed from March to April 2020, the mainstream of the second and third waves was B.1.1.284 and B. It was found that the infection spread in Japan according to 1.1.214 (reported on January 14, 2021 4) ). Furthermore, there is concern about the influx of a new mutant strain VOC-202012 / 01 that occurred in the United Kingdom, and not only airport quarantine inspections but also cases showing suspicion of community-acquired infection have been published.
There are three mutant strains characterized by multiple mutations in the Spike protein based on the country of origin [UK VOC-202012 / 01 (B.1.1.7), South Africa 501Y.V2 (B.1.351), Brazil 501Y.V3 (P) .1)] has been reported. It has been pointed out that the mutant strain has the possibility of immune escape that increases the transmission power and diminishes the vaccine effect, and is closely watching the influx into the country and the transmission of the infection. For details on the characteristics of the mutant strain, see the risk assessment report on the website of the National Institute of Infectious Diseases, "New mutant strain of the new coronavirus (SARS-CoV-2), which is concerned about increased infection / transmission and changes in antigenicity (No. 1). Please refer to 5 ) ” 5) .
The Spike protein covers the surface of the coronavirus and binds to human receptors (ACE2 protein in the case of the new corona). Neutralizing antibodies that have an affinity for the receptor-binding domain (RBD, 328–533aa) are known to be most effective in protecting against infection 6) . The mutant strain has characteristic mutations in 2-3 positions of RBD (N501Y, E484K, K417T / N), and in particular, glutamic acid (E) at amino acid 484 is important for ACE2 binding of RBD and is a neutralizing antibody. It is an amino acid residue located at the central epitope of. Glutamic acid (E) is an acidic polar side chain amino acid that exhibits a negative charge, while lysine (K) is classified as a basic amino acid that exhibits a positive charge. In other words, the E484K mutation is a remarkable mutation that reverses the polarity that reverses the NS pole of the magnet and is noteworthy. Although the vaccine is not ineffective with this E484K alone, it has been pointed out that the effect may be diminished in no small measure 7-9) .
Domestic diffusion of strains carrying the Spike protein E484K mutation (Pangolin B.1.1.316)
E484K mutation to the same Spike protein as the mutant strains (N501Y.V2 and N501Y.V3) reported in South Africa and Brazil from the beginning of December 2020 onwards in the national survey of COVID-19 genome surveillance * 3. B.1.1.316 strain (2 cases of airport quarantine, 91 cases throughout Kanto area) was detected (as of 02/02/2021).
The B.1.1.316 strain does not have the N501Y mutation, which is a mutation that may increase infectivity and transmission, and it is presumed that the phenotype is different from that of the mutant strain having the N501Y mutation.
According to the evaluation of the genome network diagram , this B.1.1.316 is not at least the genealogy of the current two mainstream strains in Japan, but a 13-base mutation (approximately 7) from the European strain (B.1.1.114) from March to April 2020. There was a time difference of months). The sample that fills the blank link of this 13-base mutation in the domestic sample has not been specified, and it was judged that the genealogy did not acquire the mutation in Japan. In addition, a search for all GISAID registered genomic information has not identified the country of origin indicating the origin of this influx B.1.1.316 strain (that is, the region such as the United Kingdom cannot be determined). On the other hand, no strains that have acquired the E484K mutation from two mainstream strains in Japan (B.1.1.284 and B.1.1.214) have been detected so far.
in conclusion
Vaccination will be started in Japan as well. Although it is an important tool for suppressing transmission of infection, it is necessary to pay close attention to adaptive mutation of the virus after vaccine introduction. In addition to efforts to curb the spread of infection in Japan, it is also important to detect the domestic influx of strains of global concern or the emergence of mutant strains in Japan at an early stage. In order to deal with these issues, it is important to establish a systematic and continuous genome surveillance.
* 1 Global Initiative on Sharing All Influenza Data (GISAID) 10) .
GISAID is an information database of influenza virus established by medical researchers in August 2006 when bird flu raged. GISAID also independently manages, registers and collects SARS-CoV-2 genomic information. Pathogen gene information is acquired from a certain number of samples every year to investigate the outbreak trends over the years, and it is used for transmission status and vaccine strain selection. - genetic characteristics of 1,000 shares / year as of vaccine antigen (hemagglutinin HA) of Japan of influenza virus (A / H1 and A / H3) and anti-influenza virus drugs inhibit target (neuraminidase NA) it has been registered.
* 2 COVID-19 Lineage Assigner Phylogenetic Assignment of Named Global Outbreak LINeages (Pangolin)
Molecular phylogenetic analysis ID based on genomic information of the new coronavirus ( https://cov-lineages.org/lineages.html )
* 3 COVID-19 Genome Surveillance
This survey cannot be wiped out as an evaluation with regional bias. Therefore, we believe that further additional investigation is essential for the most recent positive specimens as much as possible.
Acknowledgments: We would like to express our deep gratitude to those involved in medical institutions, health centers, and government agencies for their cooperation in the survey such as sample collection.
This research is conducted by AMED (Research Project Number: JP19fk0108104, JP20fk0108103) of the Japan Medical Research and Development Organization and the project cost of the welfare labor administration promotion research project. This was carried out with the research support of "Development and research of infectious disease epidemiological methods" (group leader, Motoi Suzuki, division, Makoto Kuroda).
There are no companies in conflict of interest that should be disclosed in relation to this paper.
