Thailand Medical News - For All The Latest Breaking Medical News, Health News, Research News, COVID-19 News, Outbreak News, Dengue News, Glaucoma News, Diabetes News, Herb News, Phytochemical News, Heart And Cardiology News, Epigenetic News, Cancer News,

Nikhil Prasad  Fact checked by:Thailand Medical News Team Dec 13, 2023  2 months, 1 week, 4 days, 12 hours, 21 minutes ago

COVID-19 News University Of Minnesota Study Finds That Lys417 Acts As A Molecular Switch That Regulates The Conformation Of SARS-CoV-2 Spike Protein

facebook sharing button Share
twitter sharing button Tweet
linkedin sharing button Share
COVID-19 News University Of Minnesota Study Finds That Lys417 Acts As A Molecular Switch That Regulates The Conformation Of SARS-CoV-2 Spike Protein
Nikhil Prasad  Fact checked by:Thailand Medical News Team Dec 13, 2023  2 months, 1 week, 4 days, 12 hours, 21 minutes ago
COVID-19 News: The COVID-19 pandemic caused by SARS-CoV-2 has posed unprecedented challenges to global health, leading researchers to delve deep into the molecular intricacies of the virus. Among the critical players in viral entry and immune response is the spike protein, which has now become the focus of an intriguing study conducted by researchers at the University of Minnesota Medical School, USA.

Identification of residue 417 as a molecular switch that regulates the conformation of SARS-CoV-2 spike.
(A) Structure of trimeric SARS-CoV-2 spike ectodomain in the closed conformation with three receptor-binding domains (RBDs) down (PDB 6VXX). Each monomeric subunit of the spike trimer is colored differently. The RBD contains a core structure (in cyan) and a receptor-binding motif (RBM; in magenta). Lys417 in the RBD is shown as blue sticks. (B) A hydrogen bond is formed between the side chain of Lys417 from one spike subunit and the main chain of Asn370 from another spike subunit, stabilizing the trimeric spike in the closed conformation. (C) Residue 417 is a valine in SARS-CoV-1 spike and has been a mutational hotspot in later SARS-CoV-2 variants.

This study covered in this COVID-19 News report, unveils a significant molecular switch, Lys417, residing in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, shedding light on its dual roles in regulating the spike's conformation and, consequently, its impact on viral infectivity and immune evasion.
Understanding the Viral Landscape
Coronaviruses have been known to infect humans, with varying degrees of virulence. SARS-CoV-2, the causative agent of COVID-19, distinguishes itself with intermediate virulence, leading to a wide spectrum of clinical manifestations in infected individuals. The virus's ability to cause mild or asymptomatic cases, delayed symptom onset, and prolonged viral shedding contributes to its rapid global spread, underscoring the need to comprehend the molecular determinants driving COVID-19.
The SARS-CoV-2 spike protein plays a pivotal role in the infection process, orchestrating viral entry into host cells and acting as a major target for the host immune response. Early in the pandemic, researchers observed that the spike protein exists in two conformations: an open state, where the RBD is exposed, and a closed state, where the RBD is buried. While much has been uncovered about the spike's exceptional binding affinity for the ACE2 receptor and its proteolytic activation, the factors governing the conformational changes remained elusive.
Identifying the Molecular Switch: Lys417
In this groundbreaking study, the study team employed cryo-electron microscopy (cryo-EM) and biochemical approaches to unravel the mystery of the SARS-CoV-2 spike conformational changes. By comparing the sequences of SARS-CoV-2 and its predecessor, SARS-CoV-1, the researchers honed in on residue 417 in the RBD as a potential key player. In the closed conformation of SARS-CoV-2 spike, Lys417 forms a crucial hydrogen bond, stabilizing the trimeric spike structure.
; Contrastingly, SARS-CoV-1, with a valine at the corresponding position, lacks this stabilizing interaction.
To test their hypothesis, the researchers introduced a K417V mutation, altering Lys417 to Val417 in the SARS-CoV-2 spike. The cryo-EM analysis of the mutated spike revealed a higher prevalence of the open conformation, validating the researchers' conjecture that Lys417 serves as a molecular switch, influencing the spike's conformation.
Impact on ACE2 Binding and Viral Entry
The study explored the consequences of the K417V mutation on the SARS-CoV-2 spike's ability to bind to the ACE2 receptor and mediate viral entry. Surprisingly, the mutation exhibited a dual effect. While weakening the direct binding of the RBD to ACE2, it simultaneously enhanced the overall binding of the trimeric spike to ACE2, facilitating more efficient viral entry.
The delicate balance struck by this mutation raises intriguing questions about how SARS-CoV-2 may have evolved to optimize infection potency while evading immune detection. Residue 417 emerges as a viral mutational hotspot, suggesting that the virus might be continually adapting to find an equilibrium between infectiousness and immune evasion, contributing to the ongoing pandemic.
Unraveling Immune Evasion Strategies
The study delves into the realm of immune evasion by analyzing the impact of spike conformation on neutralizing antibodies. The researchers identified distinct epitopes on the RBD that are accessible only in the open spike conformation. This revelation implies that SARS-CoV-2 strategically evades neutralizing antibodies by adopting the closed spike conformation, which is less susceptible to antibody recognition.
The K417V mutation, by favoring the open conformation, renders the virus more exposed to neutralizing antibodies. This intricate dance between spike conformations highlights the virus's ability to navigate the host immune response, offering a potential explanation for the observed variability in COVID-19 symptoms and immune reactions.
Implications for COVID-19 Pathogenesis and Evolution
The study's findings provide valuable insights into the structural dynamics of the SARS-CoV-2 spike protein, offering a comprehensive understanding of how molecular switches, such as Lys417, influence viral behavior. The balance between open and closed spike conformations emerges as a critical factor in shaping the virus's infectivity and immune evasion strategies.
The researchers postulate that SARS-CoV-2 may have evolved to strike a delicate balance between infection potency and immune evasion. This balance, governed in part by residue 417, could explain the unique characteristics of COVID-19, including mild or asymptomatic cases, delayed symptoms, and prolonged viral shedding.
In conclusion, the study unveils the intricate molecular interaction orchestrated by Lys417 in the SARS-CoV-2 spike protein. This molecular switch, identified through a combination of cryo-EM, biochemical, and functional analyses, emerges as a key determinant in regulating the spike's conformational changes. The delicate equilibrium between open and closed conformations influences the virus's ability to bind to ACE2, mediate viral entry, and evade the host immune response.
The implications of this study extend beyond understanding the pathogenesis of COVID-19. The dynamic interplay between the SARS-CoV-2 spike conformations provides a glimpse into the virus's evolutionary strategies. The continual adaptation, as reflected in mutational hotspots like residue 417, underscores the virus's ability to navigate the complex landscape of host-pathogen interactions.
As the world continues its battle against the COVID-19 pandemic, unraveling the molecular intricacies of the virus becomes paramount. The study not only contributes significantly to the scientific understanding of SARS-CoV-2 but also paves the way for potential therapeutic interventions targeting the viral spike protein. In this ongoing saga of viral evolution and host response, every revelation brings us one step closer to mitigating the impact of COVID-19 on global health.
The study findings were published in the peer reviewed journal: eLife.
For the latest COVID-19 News, keep on logging to Thailand Medical News.


Jun 10, 2023  9 months ago
COVID-19 News - DNA Methylation - Asymptomatic SARS-CoV-2 Infections
Sep 08, 2022  1 year ago
Source- Medical News - COVID-19 Research - Impaired Pain Modulation
Aug 04, 2022  2 years ago
Source: Medical News - SARS-CoV-2 & Cancer
Aug 13, 2020  4 years ago
Source: Supplements For COVID-19
May 10, 2020  4 years ago
COVID-19 Supplements