＞学とみ子自身が紹介したLancetの論文での表現をいくつかピックアップしてみます。 ① This result suggests that 2019-nCoV might also use angiotensin-converting enzyme 2 (ACE2) as a cell receptor. ACE２を細胞にある受容体＊として ② the binding of the SARS-CoV receptor-binding domain to the ACE2 receptor were variable 直訳：ACE2受容体へのSARS-CoV受容体結合ドメインの結合は ③ bind to, such as ACE2 for SARS-CoV2 SARS-CoV2がACE2に結合するのと同様に ④ we suggest that 2019-nCoV might use ACE2 as the receptor, ACE2を受容体として ⑤ 2019-nCoV could employ the ACE2 receptor, 直訳：ACE2受容体を使う 意訳：ACE2を受容体として使う ⑥ use angiotensin-converting enzyme 2 (ACE2) as a cell receptor. ACE2を細胞にある受容体として ②と⑤で、「ACE2 receptor」直訳すると「ACE2受容体」という言葉を使っていますが、他の表現は「ACE2を受容体として使っている」という表現ですね。この②と⑤の表現で間違えたのでしょうかね。
コスモ・バイオのSIN社2019年型コロナウイルス研究試薬のページにコロナウイルスのスパイク（S1,S2)がACR2という酵素に結合する図があります。 この図の下に「2019-nCoV は、ヒトACE2受容体を介してヒト呼吸上皮細胞に感染すると報告されています。」との説明があります。参考文献 Xu, X., Chen, P., Wang, J. et al., Evolution of the novel coronavirus from the ongoing Wuhanoutbreak and modeling of its spike protein for risk of humantransmission Science China Life Sciences pp 1–4 Sci. China Life Sci. (2020). https://doi.org/10.1007/s11427-020-1637-5 を挙げていますので、この文献のACE2に結合する部分の表現をピックアップしますと ① the Wuhan CoV would infect humans via binding of S-protein to ACE2 S-蛋白のACE2に結合する部分を介して ② via binding of S-protein to ACE2 同上 ③ We performed structural modeling of its S-protein and evaluated its ability to interact with human ACE2 molecules. ヒトACE2分子との相互作用の能力を評価した ④ according to the crystal structure of SARS-CoV S-proteinRBD domain complexed with its receptor ACE2 (PDB code:2AJF), その受容体であるACE2 ⑤ the 3-D complex structure of the Wuhan CoV S-protein binding to human ACE2 was modeled with 武漢コロナウイルスのS-タンパクのヒトACE2への結合の３次元構造がモデルで… となります。コロナウイルスが結合するのはACE2であるとしています。 したがって、このコスモ・バイオのページの日本語の「ヒトACE2受容体」という表現はあまりいいものではなく「ヒトACE2」としたほうがいいかと思います。こちらの分野では通用するのかもしれませんが、それでもウイルスが結合するのはACE2という酵素です。
A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses Kailang Wu,
Host receptor recognition by viruses is the first and essential step for viral infections. During the long history of evolutionary battles between viruses and hosts, viruses have evolved complex strategies for their receptor selections (2). Despite tremendous efforts to understand these strategies, the current picture of how viruses recognize their host receptors is still murky. Viruses exploit a wide variety of host cell surface molecules as their receptors. In addition to serving as receptors for viruses, these molecules are implicated in various host physiological functions such as cell adhesion, immune response, signaling pathways, proteolysis, and ion transport. On one hand, several viruses can share one host receptor. For example, coxsackievirus-adenovirus receptor, an immunoglobulin (Ig) superfamily member, is the receptor for both coxsackieviruses and adenoviruses (3). On the other hand, one virus can recognize several different host receptors. For example, herpes simplex viruses use one of at least three protein receptors: HVEM, which is a tumor necrosis factor receptor family member (23), and nectin-1 and nectin-2, both of which are Ig superfamily members (8, 31). Understanding the pattern of host receptor recognition by viruses has important implications for viral evolution, pathogenesis, host range, tropism, cross-species infections, emerging viral epidemics, and virus-mediated gene targeting.
A key question regarding the evolution of host receptor recognition by viruses is what features of these receptor molecules make them targeted by viruses. The receptors for viruses can be proteins, carbohydrates, or lipids (2). Compared with carbohydrates and lipids, protein receptors in general have more structural features and thus are engaged in more-specific and high-affinity binding interactions with viruses; they are the focus of this study. Among protein receptors, some (such as cell adhesion molecules) are more abundant than others (such as proteases and ion transporters). Although the availability of abundant protein receptors to viruses is probably one of the reasons why they were selected by viruses as receptors (30), it is not clear whether receptor proteins, especially nonabundant receptor proteins, contain any structural features that make them targeted by viruses.
The structural features of receptor proteins can be identified from the atomic structures of virus/receptor interfaces. Defined structural and functional receptor-binding domains (RBDs) have been identified in many viral surface glycoproteins. One or more receptor-binding motifs (RBMs) on these viral RBDs mediate the interactions with their receptor proteins. To date several crystal structures are available for viral RBDs complexed with their receptor proteins (1, 4, 5, 13, 18, 32, 33). Among these structures, only two reveal how different viral RBDs can bind to their common receptor protein: the structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) RBDs, each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2) (18, 32). Both NL63-CoV and SARS-CoV are important human viral pathogens. The former causes prevalent respiratory diseases (6, 29), whereas the latter was responsible for the worldwide epidemic of severe acute respiratory syndrome (SARS) diseases in 2002 to 2003 (12, 24). Coronavirus spike glycoproteins are envelope-anchored clove-shaped trimers (16). Each spike trimer contains three monomeric S1 heads, which function in receptor binding, and a trimeric S2 stalk, which functions in fusing the viral envelope and host membrane. NL63-CoV and SARS-CoV RBDs are located in the S1 heads of their respective spike proteins. There is no structural homology in their RBD core structures or RBMs (Fig. 1). The core structures of NL63-CoV and SARS-CoV RBDs are a two-layer β-sandwich and a single-layer β-sheet, respectively; the RBMs of NL63-CoV and SARS-CoV are three discontinuous short loops and one continuous long subdomain, respectively. Nevertheless, the two viral RBDs bind to the same three virus-binding motifs (VBMs) on hACE2 (18, 32).
J Virol. 2020 Jan 29. pii: JVI.00127-20. doi: 10.1128/JVI.00127-20. [Epub ahead of print]
Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS.
Wan Y1, Shang J1, Graham R2, Baric RS2, Li F3.
Recently a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by SARS coronavirus (SARS-CoV). Since SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV, and may help epidemic surveillance and preventive measures against 2019-nCoV.SignificanceThe recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002-2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.