MERS Coronavirüs’ün Yakın Yarasa Virüs Akrabalarında Beklenmedik Bulgu – apk haber

Meyve Yarasası Kapat

Orta Doğu Solunum Sendromu (MERS) koronavirüsünün en yakın yarasa virüsü akrabaları, insan hücrelerindeki ACE2 reseptörleriyle bazı benzerliklere sahip olan bu hücrelere bir giriş noktası olarak yarasa ACE2 reseptörlerine etkili bir şekilde bağlanıyor. dergi Doğa.

Yarasa Virüsü Reseptörü Çalışmaları Yayılma Riskini Tahmin Etmek İçin Hayati

Son araştırma, beklenmedik bir şekilde, insan solunum virüsü MERS-CoV’nin iki yakın yarasa virüsü akrabasının hücre giriş reseptörü olarak yarasa ACE2’yi kullandığını gösteriyor.

Yeni araştırmaya göre, insan Orta Doğu Solunum Sendromu (MERS) koronavirüsünün en yakın yarasa virüsü akrabaları, bu hücrelere giriş noktası olarak yarasa ACE2 reseptörlerine verimli bir şekilde bağlanır. Bu reseptörler, insan hücrelerindeki ACE2 reseptörleri ile bazı benzerliklere sahiptir.

Bununla birlikte, şu anda NeoCoV olarak adlandırılan bu koronavirüs ve benzer bir virüs olan PDF-2180, hücrelere giriş noktası olarak insan ACE2 hücre reseptörlerine yalnızca zayıf bir şekilde bağlanmaktadır. Ayrıca insanlarda hastalık salgınlarına neden oldukları bilinmemektedir.

Bu son araştırmayı bildiren bilim insanları, “Bugüne kadar, NeoCoV ve PDF-2180’in yarasalar dışında herhangi bir memeliye bulaşabileceğine dair hiçbir kanıt yok.

Çarpıcı bir şekilde, MERS koronavirüsü, diğer birkaç ilgili, iyi karakterize edilmiş merbecovirüs gibi, DPP4 (dipeptidil peptidaz-4) adı verilen tamamen farklı bir hücre reseptörü kullanır.

Merbecovirus, insan patojeni Orta Doğu solunum sendromu ile ilişkili koronavirüs (MERS-CoV) dahil olmak üzere Betacoronavirus cinsindeki virüslerin bir alt cinsidir.

Bir anjiyotensin dönüştürücü enzim reseptörü olan insan ACE2, insanlarda enfeksiyonlar için ana hücre giriş reseptörüdür.[{” attribute=””>SARS-CoV-2, the coronavirus that causes COVID-19. It is also the human cell receptor for SARS-CoV-1, the cause of Severe Acute Respiratory Syndrome, identified in 2003 after a pneumonia outbreak later confirmed to have jumped across species.

Overall, many other sarbecoviruses, an alphacoronavirus (setracovirus), and a group of merbecoviruses share the ability to bind to ACE2 in the cells of certain animals. The convergent evolution that led widely different coronaviruses to use ACE2 as entry receptors remains unclear.

Cryo-electron microscopy analysis revealed that NeoCoV has a distinct way of binding with the bat ACE2 receptor, compared to the other coronaviruses known to use that receptor.

The findings of this research, conducted by an international team of scientists, appear in the December 7 edition of Nature. The senior and corresponding authors of the paper are David Veesler, associate professor of biochemistry at the University of Washington School of Medicine in Seattle and an investigator of the Howard Hughes Medical Institute; Xiangxi Wang of the Institute of Biophysics at the Chinese Academy of Sciences in Beijing, and Huan Yan of the College of Life Sciences at Wuhan University.

David Veesler

David Veesler at a microscope in his biochemistry lab at the University of Washington School of Medicine. Credit: Randy Carnell/UW Medicine

Discovering that ACE2 is the host cell receptor for NeoCoV and PDF-2180, which are closely related to the deadly human pathogen MERS-CoV, was totally unexpected and opens new avenues to prepare for the possible future zoonotic transmission of these viruses, according to the researchers on this study. This information is critical in setting up a watch-list of families of animal viruses that present a risk of emerging as zoonotic diseases in people.

The lack of knowledge about which cell receptors bat coronaviruses use, the researchers explained, limits scientific understanding of their cell entry strategies and of the virus’ propensity for interspecies transmission.

Observing the complexities of how coronaviruses use cell receptors, the researchers noted in their paper, highlights the importance of additional research and surveillance on these viruses to stay ahead and be prepared for future outbreaks.

The researchers on this current study also sought to gather data that might provide clues to the origin of MERS-CoV. Their results support earlier hypotheses that MERS-CoV may have appeared after a recombination event between a virus that was like NeoCoV and a virus that preferred the DPP4 cell receptor.

While the history of this event has not been confirmed, the scientists surmised that such genetic recombination in viruses can happen when a host animal is co-infected with different coronaviruses. In this way a new coronavirus can emerge, using a distinct cell receptor with possible expansion of host range.

For MERS-CoV, the scientists noted that it remains uncertain whether such an event could have occurred in bats, camels, or other animals, or when the switch to a new animal (or human) host could have taken place.

The two viruses, NeoCoV and PDF-2180, prefer the ACE2 cell receptors in vesper bats, part of the species Vespertilionidae. Most merbecoviruses are found in that species. This is a remarkably diverse, widely dispersed bat species.

While NeoCoV does not have a strong affinity for the ACE2 receptor on human cells, the scientists pointed out NeoCoV could undergo adaptive changes that would allow it to enter human cells more readily. The extensive mutations in the key cell binding regions of the COVID-19 virus (SARS-CoV-2), particularly in the Omicron variant, indicate that other coronaviruses may hold the still unrealized ability to adapt through mutations.

On the other hand, spillover of viruses from one animal species to another is a complicated transition that involves not just recognizing a cell receptor in the jumped-to species, but also subverting host immune responses, contact opportunity, conditions suitable for the virus to replicate, and many other factors.

The researchers also mentioned that MERS-CoV antibodies and antibodies generated by current COVID-19 vaccinations do not adequately neutralize NeoCoV and PDF 2180. However, their results showed that broadly neutralizing antibodies that target evolutionarily conserved regions of NeoCoV and PDF-2180 do inhibit the entry of these viruses into cell. They suggest that these broader-acting antibodies should be considered for preparedness against spillover to humans by these viruses.

Reference: “Close relatives of MERS-CoV in bats use ACE2 as their functional receptors” 7 December 2022, Nature.
DOI: 10.1038/s41586-022-05513-3

This research was supported by the National Natural Science Foundation of China (32188101, 32270164 and 32070160), Fundamental Research Funds for the Central Universities (2042020kf0024) and a Special Fund for COVID-19 Research of Wuhan University, the Strategic Priority Research Program (XDB29010000 and XDB37030000), Chinese Academy of Sciences (YSBR-010), National Key Research and Development Program (2020YFA0707500 and 2018YFA0900801), Beijing Natural Science Foundation (Z210014), the Ten Thousand Talent Program and the NSFS Innovative Research Group (81921005). The research project was also funded in part by the National Institute of Allergy and Infectious Diseases (DP1AI158186 and 75N93022C00036), a Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund, Fast Grants, the University of Washington Arnold and Mabel Beckmancryo-EM center, the National Institute of Health (S10OD032290).

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