Scientists Warn SARS-CoV-2 Infections In Animals Are Turning Out Mutations That Are Detrimental To Humans Such As The Leu452Met Amino Acid Exchange!

The SARS-CoV-2 virus is replicating and evolving in animals and churning mutations that are detrimental to humans including the amino acid exchange Leu452Met that could totally undermine acquired immune protection in humans while maintaining high affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor.
 
Thailand Medical: The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has wreaked havoc on global health, leading to millions of deaths worldwide. As the virus continues to spread and evolve, scientists are growing increasingly concerned about the potential for animal-derived mutations to worsen the pandemic. Researchers from Fudan University in Shanghai-China, Free University Berlin in Germany, University of California Los Angeles, and David Tulane University in the USA have jointly conducted groundbreaking research to shed light on this pressing issue.


Surface representation of the receptor-binding domain of S from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The amino acids making up the four classes of human antibody epitopes are colored blue (class 1), magenta (2), orange (3), or green (4). Amino acids colored cyan are shared by class 1 and 2 epitopes. Unique amino acid exchanges in the spike of SARS-CoV-2 from animals are colored red and are labeled. The ACE2-binding site is on top of the molecule

The Impact of Animals in the Evolution of SARS-CoV-2
In the early stages of the pandemic, it was discovered that various animals were susceptible to SARS-CoV-2 infection, including domestic pets like dogs and cats, as well as wild animals such as minks and white-tailed deer. Human-animal contact, whether through pets or interactions with wildlife, has facilitated the transmission of the virus across species barriers. This increased overlap of human and animal habitats has created potential hotspots for virus spillover and subsequent evolution.
 
The Concerning Role of Mink and White-Tailed Deer
Mink and white-tailed deer have emerged as critical species in the transmission and potential adaptation of SARS-CoV-2. Mink farms have experienced widespread infections, prompting concerns about sustained transmissions leading to virus evolution within the mink population. White-tailed deer, with their wide distribution overlapping human habitats, have also been infected with multiple SARS-CoV-2 variants, including the Alpha and Delta variants. These instances highlight the possibility of viruses circulating between animals and humans, creating reservoirs for the virus's evolution.
 
Unique Mutations in Animal-Derived SARS-CoV-2
The researchers identified nine unique amino acid exchanges in the receptor-binding domain (RBD) of the spike protein, which are not present in any variant of concern (VOC) and found in animal-derived SARS-CoV-2 sequences. These mutations were observed in animals such as dogs, cats, mink, and white-tailed deer. Among the identified mutations, Leu452Met is of particular concern as it could totally undermine acquired immune protection in humans while maintaining a high affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor.
 < ;br /> Potential Threat to Human Immune Protection
The spike protein's amino acid exchange, Leu452Met, has raised serious concerns about its potential impact on human immune protection. The mutation may reduce the virus's susceptibility to neutralizing antibodies, leading to the evasion of acquired immunity from prior infections or vaccinations. This situation could significantly impact public health efforts to control the spread of the virus.
 
The Need for One Health Programs and Surveillance
To address the emerging threat of animal-derived mutations, researchers advocate for the establishment of One Health programs. These programs would closely monitor wild, farm, and domestic animals, as well as their trade routes, to track the virus in animal populations and assess the risk of cross-species transmission.
 
Technological Advances in Assessing Virus Mutations
The study team told Thailand Medical News that they had developed cutting-edge techniques to assess the impact of mutations in the viral spike protein on receptor binding and antibody binding. These methods enable the rapid evaluation of the effects of key mutations and help in estimating the potential risk posed by animal-derived viruses to human populations.
 
Future Research Directions
The research team emphasizes the importance of increased surveillance, particularly through metagenomic next-generation sequencing, to rapidly identify mutations that pose a threat to public health. Additionally, further investigation into the structural basis of SARS-CoV-2's ability to infect various animals will provide critical insights into potential adaptive mutations.
 
Conclusion
The findings of this collaborative research from leading institutions raise an alarm about the potential dangers posed by animal-derived mutations of SARS-CoV-2. As the virus continues to evolve in various animal species, there is an urgent need for global cooperation and coordinated efforts to monitor and track potential threats. One Health programs and advanced surveillance technologies will play a crucial role in protecting human populations from the emergence of new variants. By staying vigilant and proactive in our approach, we can mitigate the risks and work towards overcoming this unprecedented global health challenge.
 
The study findings were published in the peer reviewed journal: Trends in Microbiology
https://www.cell.com/trends/microbiology/fulltext/S0966-842X(23)00199-3
 
More About Leu452Met Mutation
The Leu452Met mutation is a specific amino acid exchange in the receptor-binding domain (RBD) of the spike protein of the SARS-CoV-2 virus. This mutation involves the substitution of leucine (Leu) with methionine (Met) at position 452 in the RBD. The RBD is a crucial part of the spike protein responsible for binding to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is the entry point for the virus into human cells.
 
The significance of the Leu452Met mutation lies in its potential to impact both the virus's ability to evade the human immune system and its affinity for the ACE2 receptor. Several studies have indicated that mutations in the RBD can affect the virus's transmissibility and its susceptibility to neutralizing antibodies, which are essential for immune protection.
 
The Leu452Met mutation, in particular, has been of concern to researchers because it may totally undermine acquired immune protection in humans. This means that individuals who have previously been infected with SARS-CoV-2 or have received vaccinations might no longer be protected against the virus if it carries this specific mutation. By evading the immune response, the virus can potentially cause reinfections and totally reduce the effectiveness of existing vaccines.
 
Moreover, the Leu452Met mutation is thought to maintain a high affinity for the human ACE2 receptor. This could enhance the virus's ability to enter human cells more efficiently, leading to increased infectivity and potentially higher transmission rates.
 
It's important to note that the Leu452Met mutation is just one of several mutations that have been identified in the spike protein of SARS-CoV-2. The virus's high mutation rate enables it to continuously adapt and evolve, potentially leading to the emergence of new variants with altered properties.
 
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