Distinct spike protein mutations in SARS-CoV-2 variant in Russia

By Marzia KhanJun 7 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus 2019 (COVID-19) pandemic, has lasted for approximately a year and a half, with over 173 million infections reported worldwide.

In spite of having acquired and identified a large number of genetic sequences and variants since the start of the pandemic, scientists still face the challenge of identifying new variants of concern.

The genetic variants of concern include the UK (20I/501Y), Brazil (20J/501Y.V3), and South Africa (20H/501Y.V2).

Additionally, a novel variant has recently been characterized by researchers from Russia in the journal Viruses. The variant, first discovered in January 2021 in Northwest Russia, is characterized by distinct spike protein mutations.

Study: Characterization of a Novel SARS-CoV-2 Genetic Variant with Distinct Spike Protein Mutations. Image Credit: Kateryna Kon / Shutterstock

Genetics of SARS-CoV-2

The information available about SARS-CoV-2's genetic diversity in Russia is relatively conservative because only a limited number of sequences have been uploaded to genetic databases such as NCBI GenBank and GISAID.

The database GISAID has outlined that the most common genetic variants in Russia belong to the 20B clade.

The SARS-CoV-2 virus consists of genes such as S, E, M and N, which encode structural proteins, with the ORF 1a and ORF 1b regions encoding non-structural proteins including 3-chymotrypsin-like protease, papain-like protease, and RNA-dependent RNA polymerase.

The S protein includes an extracellular N-terminus, a transmembrane domain in the viral membrane and a short intracellular C-terminus; this protein can undergo structural rearrangement when the SARS-CoV-2 virus interacts with the host cell, enabling the virus to fuse with the host cell membrane.

The authors of this paper describe the results of two genome sequences performed during routine studies of the genetic diversity of variants found in Northwest Russia, which have been found to be genetically different when compared to the gene that encodes the virus' S protein.

Findings

The analysis of the genetic sequences obtained illustrates distinct mutations in two sequences located in the spike glycoprotein gene. These mutations both include a 27-nucleotide deletion at positions 21,967-21,993 and a 12-nucleotide insertion at positions 23,598-23,599.

Structural model of variant SARS-CoV-2 S protein, SPb-117 strain (NW), based on PDB:7cwu.1 structure [24]. Black arrows indicate the positions of the main mutations of the described strain: the deletion of nine amino acids, C136_Y144del (Wuhan-Hu-1 strain numbered residues); and the insertion of four amino acids, N679delinsKGIAL. Both mutations lie in protruding regions of the amino acid chain.

The main distinctive feature of the Northwest Russian variant is a difference in the S protein amino acid composition, however, these changes do not affect the overall structure of the protein.

Furthermore, other analyses have revealed mutations that affected the cleavage sites of the variant, affecting its entry into the host cell, as well as mutations affecting the clathrin-coated vesicle, which may have affected viral entry.

The importance of clathrin-coated vesicle formation lies in its prominent role in vesicular traffic that reaches the endosomal compartment. The binding of the virus to the angiotensin-converting enzyme 2 (ACE2) enables the formation of clathrin-coated pits; this is significant for clathrin-mediated endocytosis used by SARS-CoV-2, as confirmed by a 2021 study mentioned in this paper.

The research describes the identification of a new, previously-undescribed SARS-CoV-2 variant, which we have termed the Northwest Variant (NW variant). In light of the significant differences in the outer region of the S protein, it can be assumed that the properties of the NW variant will be significantly different from those of the other variants. Thus, the NW variant might be a variant of concern (VOC). However, this assumption needs to be more rigorously examined.

Characterization of this novel Northwest Russian variant is integral for the up-keep of global research into emerging variants by the science community in order to competently understand and treat the infection effectively. These genetic mutations enable more knowledge on how the virus works and in what ways the variants are mutating the core virus. It will inform the research of vaccines and novel therapeutics that can be made to ensure these genetic mutations are also considered.

The researchers have shown how the genetic mutations of two SARS-CoV-2 sequences affect the spike protein gene, which can change the receptor affinity to ACE2.