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Article by Dr. Than Thi Trang Uyen - Medical Specialist - Stem and Immune Cells - Production Project Department - Vinmec Stem Cell Research Institute and Gene Technology.The current public health emergency is partly akin to the emergence of the SARS outbreak in southern China in 2002. Both occurred in winter with initial cases associated with exposure to animals Live animals are sold at animal markets and both are caused by previously unknown coronaviruses.
Wuhan Municipal Health Commission reported the first cases of acute pneumonia concentrated in Wuhan city, Hubei province of China on December 30, 2019. The pneumonia cases were found to be linked to a seafood and animal market in Wuhan.
The Centers for Disease Control and Prevention (CDC) and Chinese health authorities later identified and announced that a new coronavirus called Wuhan CoV (2019-nCoV) had caused an outbreak of pneumonia in China. this city. The current public health emergency is partly like the emergence of the SARS epidemic in southern China in 2002. Both occurred in winter with the first cases associated with exposure to the virus. Live animals are sold at animal markets and both are caused by previously unknown coronaviruses.
The 2019-nCoV genome sequence was first published on January 10, 2020, and was followed by many additional publications on the 2019-nCoV genome sequence. To understand the origin of 2019-nCoV and its genetic relationship with other coronaviruses, the study by Xintian Xu et al. (published January 21, 2020) performed a phylogenetic analysis based on on the coronavirus genome from various sources. The results showed that 2019-nCoV was grouped into the genus Betacoronavirus in the phylogenetic tree. Their natural host is likely bats, and that the SARS/SARS-like coronavirus (SARS-like coronavirus) shares a common ancestor with the bat coronavirus HKU9-1.
To study 2019-nCoV and their interactions with the host, the research team looked at the receptor binding domain (RBD) spike protein (S-protein) of 2019-nCoV and found several copies. patch sequences with high homology to SARS-CoV_Tor2 and HP03-GZ01. Positions 438, 472, 479, 487 and 491 of the SARS-CoV S-protein were found to be located at the receptor contact site and are considered to be critical for SARS-CoV cross-species transmission and transmission from person to person. However, only the Tyr491 site is conserved in the S-protein of 2019-nCoV, leaving four of the other five key sites that are no longer seen in 2019-nCoV.
To assess the risk of human-to-human transmission of 2019-nCoV, the team modeled the virus's protein S structure and evaluated its ability to interact with human cells' ACE2 molecules. The computational model of the Wuhan 2019-nCoV S protein shows that the square root deviation (RMSD) of Cα is 1.45 Å on the RBD domain compared with the S protein structure of SARS-CoV. The binding free energy between the S protein of 2019-nCoV and human ACE2 is -50,6 kcal/mol, while that between the S-protein of SARS-CoV and human ACE2 is -78.6 kcal/mol. Due to the loss of hydrogen-binding interactions due to replacement of Arg426 with Asn426 in the Wuhan 2019-nCoV S protein, the binding free energy for the Wuhan 2019-nCoV S protein increases by 28 kcal/mol when compared with the S protein of SARS-CoV. This result indicates that the RBD domain of the S protein on 2019-nCoV Wuhan supports a strong interaction with human ACE2 molecules. Therefore, Wuhan 2019-nCoV poses a significant risk of community transmission through the association of the 2019-nCoV S-protein with ACE2 on the surface of human cells.
References:
Xintian Xu, Ping Chen, Jingfang Wang, Jiannan Feng, Hui Zhou, Xuan Li, Wu Zhong & Pei Hao. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China, Life Sciences, Jan 2020.
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