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L452R mutations may favor adaptive evolution of SARS-CoV-2

A team of US scientists recently investigated the mutated signature of the receptor-binding domain (RBD) of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Spike protein.. The findings reveal that the frequency of L452R mutations in the spike region has increased since November 2020. The L452R mutation, which is predicted to increase viral infectivity and host immune evasion, has recently been shown to be associated with the viral variant that caused the large-scale viral mutation. Outbreak in California. Research is currently bioRxiv* Preprint server.

Background

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped RNA virus. Coronaviridae.. Apart from the original Wuhan strain that emerged in December 2019, many different variants of SARS-CoV-2, including some spike mutations, are continuously emerging throughout the pandemic process. Most of these mutants are considered “concerned mutants” because they contain mutations in the peplomer RBD and are capable of increasing the infectivity, pathogenicity, and immune evasion of the virus.

Of the two domains of the SARS-CoV-2 spike (S1 and S2) Glycoprotein, S1 interacts with the angiotensin converting enzyme 2 (ACE2) receptor in the host cell via RBD. This is followed by proteolytic dissociation of the S1 and S2 domains, followed by fusion of the viral envelope with the host cell membrane. Since RBD is heavily involved in virus recognition and invasion, structural changes in this area due to mutations can affect the infectivity and pathogenicity of the virus. In addition, antibodies developed against RBD have been shown to be most effective in neutralizing SARS-CoV-2.

In the current study, scientists analyzed genetic alterations in the 414-583 amino acid region of the spike S1 domain, which partially covers RBD. Analyzing a total of 570 nasopharyngeal specimens collected from COVID-19 patients from different parts of the United States between April 2020 and February 2021 using the polymerase chain reaction (PCR) and Sanger sequencing. Did.

Distribution of silent (green triangle) and amino acid (red triangle) mutations throughout the region 414-583 of peplomer. Dark red – receptor binding domain (RBD); green – C-terminal domain 1 (CTD1) in the S1 spike region. Blue – Receptor-binding ridge epitope residue. Yellow – 443-450 loop epitope residue. Black – 570-572 loop residues.

Distribution of silent (green triangle) and amino acid (red triangle) mutations throughout the region 414-583 of peplomer. Dark red – receptor binding domain (RBD); green – C-terminal domain 1 (CTD1) in the S1 spike region. Blue – Receptor-binding ridge epitope residue. Yellow – 443-450 loop epitope residue. Black – 570-572 loop residues.

Important findings

Scientists have identified the L452R amino acid substitution in the spike region as a dominant mutation in specimens collected after November 2020. Specifically, we observed the recent emergence of two independent SARS-CoV-2 variants (CAL.20C and CAL.20A) containing the spike L452R mutation. In California. Of these variants, CAL.20C (Clade 20C; Strain B.1.429) has been considered the predominant variant in California since November 2020. However, the CAL.20A variant (clade 20A; strain B.1.232) identified in this study appeared much more recently than CAL.20C and is mainly distributed in California.based on Phylogenetic analysis, Scientists have shown that the L452R mutation is the main driving force behind the emergence of both mutants. This increase in L452R mutation frequency in recent SARS-CoV-2 mutants directly indicates a significant involvement in viral adaptive evolution through positive selection.

In contrast to CAL.20C, no large-scale clonal expansion was observed with CAL.20A. Studies show that CAL.20C contains two additional spike mutations along with L452R, but these are not in CAL.20A. Scientists believe that these additional mutations may be involved in increasing the adaptive effect of L452R, for which reason CAL.20A cannot achieve the same expansion rate as CAL.20C. was.

Scientists examined the Nextstrain and GISAID databases and found that, apart from the two California variants, the L452R mutation was present in more than 400 SARS-CoV-2 genomes isolated from more than 20 countries. This shows a strong positive selection of L452R mutations. Interestingly, they found a CAL.20A mutant in a gorilla at the San Diego Zoo. It contains two additional mutations in Unstructured Protein 2 (NSP2).

Based on the available literature, scientists have found that replacing the hydrophobic leucine residue at position 452 with a highly polar hydrophilic arginine residue (L452R mutation) strongly promotes the interaction between the virus and the host cell. , Said that the virus could increase significantly. Infectious and infectious. In addition, such amino acid substitutions are expected to reduce the viral neutralizing ability of antibodies that specifically target spike RBD.

Importance of research

This study demonstrates the importance of L452R mutations in the adaptive evolution of viruses. A strong positive selection of L452R mutations has been observed particularly recently, indicating that adaptive evolution of the virus may have occurred in response to extensive containment measures or increased population-level immunity to the original viral strain. I will.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.

L452R mutations may favor adaptive evolution of SARS-CoV-2

Source link L452R mutations may favor adaptive evolution of SARS-CoV-2

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