Yan Huan and his team. Screenshot of the official Wechat account of the State Key Laboratory of Virology at Wuhan University

An article published on the international academic journal Nature about the research results of the State Key Laboratory of Virology at Wuhan University on Wednesday revealed MERS-related coronavirus receptor in bats for first time, which is widely believed that will further advance basic research on MERS-related coronaviruses using ACE2 receptors and lay the foundation for the development of related vaccines and antiviral drugs.

According to the official Wechat account of the State Key Laboratory of Virology at Wuhan University, the study led by Yan Huan's research team revealed that the functional receptor of two bat MERS-associated coronaviruses, NeoCoV and PDF-2180, was ACE2, and analyzed the receptor-binding complex of the two viruses and the structure of the PDF-2180 trimeric spike protein. These findings suggest a potential threat to human health and provide new support for the "bat origin" hypothesis of the MERS-CoV.

The article, entitled "Close relatives of MERS-CoV in bats use ACE2 as their functional receptors," said three kinds of beta coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, have caused three major human outbreaks this century - SARS, Middle East Respiratory Syndrome (MERS), and COVID-19. In fact, these three viruses are just the tip of the iceberg of a larger family of coronaviruses and studies of many of the potentially zoonotic coronaviruses in nature remains very limited.

Therefore, successful identification of coronavirus receptors and establishment of corresponding infection models are of great significance for revealing the law of virus infection and transmission, evaluating pathogenicity of the virus and immune response of the host, and developing vaccines and antiviral drugs.

The unexpected result aroused great attention of the research team as it broke through the conventional understanding of coronavirus receptors and revealed for the first time that MERS-associated coronaviruses could enter cells using ACE2.

MERS-CoV, the most pathogenic human coronavirus known to cause disease, was first identified in Saudi Arabia in 2012 and is mainly endemic in Middle Eastern countries. According to the latest statistics from the World Health Organization, MERS has infected 2,600 people and killed 935, with a case fatality rate of 36 percent. However, MERS-CoV is significantly less transmissible than the novel coronavirus (SARS-CoV-2), with sporadic infections occurring only in the Middle East since 2016.

Public data showed that the intermediate host of MERS-CoV is the camel, but its natural evolutionary origin is unclear. However, a growing body of evidence suggests that bats, as natural hosts of hundreds of alpha and beta coronaviruses, have played an important role in the evolution of multiple human coronaviruses, including the MERS-CoV.

According to the official website of the State Key Laboratory of Virology, the laboratory was approved by the Ministry of Science and Technology in March 2005. At present, the laboratory has the one of the international storage institutions recognized by the World Intellectual Property Organization and the China Virus Resources and Information Center, the largest virus storage bank in Asia and a complete biosafety laboratory

NeoCoV, which is found on Cape serotine samples in South Africa in 2012, is the closest coronavirus to MERS-CoV found in nature.

In the process of exploring functional receptors for several representative bat coronaviruses, the research team found that NeoCoV and PDF-2180, two pseudo viruses of MERS-associated coronaviruses, were able to enter cells expressing human ACE2 receptors with low efficiency. Angiotensin-converting enzyme 2 (ACE2) is known to be the converting enzyme for SARS-CoV-2.

The researchers then collaborated further to explore the molecular mechanisms by which the two viruses recognize the receptors and the ability of related antibodies to block the entry of pseudo viruses into cells.

It should be emphasized that it is not clear whether the MERS-related coronavirus using ACE2 can infect humans and cause outbreaks, and its pathogenicity and transmissibility still require further research.

Global Times