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Very close relatives of SARS-CoV-2 identified in Lao bats




The pandemic SARS-CoV-2 virus may be derived from Southeast Asian bats. More than 450 million people share the region with bats living in limestone caves in countries such as Vietnam, Thailand, Myanmar and Laos. One of the predominant bat genera in the region is Rhinolophus (Horseshoe-shaped bat). Bat species in this genus contain the ACE2 receptor, which closely resembles the human receptor. In fact, ACE2 is so similar that many of the coronaviruses in these bats can also infect humans.

The exact origin of the SARS-CoV-2 virus is shrouded in mystery and some controversy. Recent estimates of people infected with the horseshoe-shaped bat-derived coronavirus in Southeast Asia are between 400,000 and 2 million.recently study From Pasteur Institute, Temam et al.Investigate bat-specific viruses in this area.

The researchers sampled 645 bats from four different Lao sites. Bats have been classified into 46 different species. With over 1,400 bats around the world, it should come. They extracted the coronavirus from bat blood, feces, urine and saliva.

The first finding is that as many as seven bats carry the same type of coronavirus known as salvecovirus. These are subgenuses of the beta coronavirus, to which the SARS-CoV-2 and SARS-CoV species of viruses belong.

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With a surprising finding, the authors report that some of the viruses isolated from bat caves in Vientiane are very closely associated with SARS-CoV-2. In fact, they are so closely related that the idea that SARS-CoV-2 is derived from the RaTG13 coronavirus isolated from horseshoe-shaped bats in southern China in 2013 can no longer be supported. The receptor binding domains of SARS-CoV-2 and RaTG13 are very different.

The original SARS-CoV-2 Wuhan strain has 17 amino acid contact points between the virus and the ACE2 receptor.

Some of these have been modified by the RaTG13 coronavirus.However, two of the viruses analyzed by Temmam et al.—BANAL-20-52 and BANAL-20-103— differ in only one of the 17 amino acids. Another analyzed virus, BANAL-20-236, differs only in two amino acids. In contrast, RaTG13 has six amino acid modifications. Note that changes in only one or two residues at the contact point are well within the range of various natural variants of SARS-CoV-2 that result in as many as three amino acid changes in these residues. please.

The authors have several to determine if the receptor-binding domain region similarity of the peplomeres BANAL-20-52, 103, and 236 is converted to similar function to SARS-CoV-2. An experiment was conducted. Their first question was whether the receptor-binding domain of the virus could infect cells that carry the human ACE2 receptor. Using pseudoviruses on cells in culture, they found that the answer was certainly yes. They further showed that plaque formation occurs when the complete genome of BANAL-20-236 is introduced into human cells. In fact, it formed more plaque than the Wuhan strain of SARS-CoV-2. These two observations indicate that not only does the bat virus receptor binding domain recognize human ACE2, but the entire virus can infect humans.

Their second concern was to understand exactly how similar the bat coronavirus is to ACE2 compared to SARS-CoV-2. Using binding modeling and structural analysis, researchers show exactly how the bat virus receptor binding domain can interact with the ACE2 protein, and a biochemical explanation of how bat spikes bind. Provided. The similarities between SARS-CoV-2 and the two bat viruses are spread throughout the genome, with one notable exception. Orf8.. Among the SARS-CoV-2 mutants, Orf8 is one of the most frequently mutated genes.

To understand the functional dynamics of the interaction and relationship between the bat receptor binding domain and ACE2, researchers performed biolayer interference measurement assays on various viruses to analyze the binding affinity in the nanomolar range. Did. In layman’s terms, they tested whether the bat virus binds to ACE2 with the same tightness as SARS-CoV-2.

Finally, X-ray crystallography was used for both SARS-CoV-2 and BANAL-20-52 at a resolution of 2.9 angstroms to analyze the binding structure. The figure below shows the structural similarities and differences between the two complexes, especially the mutant residues in the receptor binding domain and the helix structural complex. As expected, most of the interactions observed between ACE2 and the SARS-CoV-2 receptor binding domain were also present in BANAL-236.

Recombination is frequently observed among naturally occurring coronaviruses. The Lao bat virus is no exception. The authors were able to decipher recombinant events between a wide range of families of coronaviruses that infect bats. This may contribute to the origin of SARS-CoV.

The image that emerges is a continuous reassortment of genes that leads to a mosaic of viruses. For both SARS-CoV-2 virus and bat virus, external peplomer appears to have two separate sources. One for the N-terminal domain and the other for the receptor binding domain.

One remaining question is the origin of the wind chime cutting site.recently Research It was found that among the viruses, there are many coronaviruses that have independently induced furin cleavage sites. Many genera of coronaviruses, such as alpha coronavirus, gamma coronavirus, and beta coronavirus, contain several viruses with naturally occurring sites. Keep in mind that some viruses with the same virus pair over their entire length may have different furin cleavage sites. For example, SARS-CoV-2 contains one, but SARS-CoV does not. In fact, furin cleavage sites are often lost simply by growing SARS-CoV-2 in human tissue culture. Furin sites can be generated by spontaneous recombination in some SARS-CoV-2 mutants and bat viruses, as in the case of SARS-CoV-2.

The authors speculate that coinfection with another bat or some other alien species may result in the acquisition of wind chimes. It should be added here that it may have been acquired by co-infection with humans in areas previously co-infected with another bat virus containing a furin cleavage site at another recombination event.

What is the importance of this discovery? As we have already experienced, the Covid-19 pandemic is not a one-off event. Humans are infected repeatedly and very often with coronaviruses, probably from bats and other species.Believed MERS-CoVFor example, camels were obtained from camels, and camels were obtained from viruses that are widespread in humans and bats in Africa.Many of the cold viruses that wipe out our population also have the following animal origins: OC43, Derived from livestock such as cows and pigs. Recently, there have been reports of canine coronavirus infection in Indonesian children. In addition, SARS-CoV-2 variants indicate that the coronavirus may continuously adapt to the host, resulting in a more infectious and highly pathogenic virus.

With regard to the current pandemic, it should be noted that new, more contagious, dangerous versions of COVID-19 may emerge. In addition to SARS-CoV-2, hundreds of millions of people are already infected with livestock and wildlife. New indications may emerge through coinfection of animals. mink.. In addition, recombination events between SARS-CoV-2 and other coronaviruses present in the human population can cause new and more dangerous forms of pandemics.





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