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      SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

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          Abstract

          Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

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          Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

          Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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            Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

            A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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              Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

              How SARS-CoV-2 binds to human cells Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al. present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction. Science, this issue p. 1444
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                Author and article information

                Journal
                Immune Netw
                Immune Netw
                IN
                Immune Network
                The Korean Association of Immunologists
                1598-2629
                2092-6685
                December 2021
                23 December 2021
                : 21
                : 6
                : e38
                Affiliations
                [1 ]Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.
                [2 ]College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
                [3 ]Technical Assistance Center, Korea Food Research Institute, Wanju 55365, Korea.
                [4 ]Research Group of Functional Food Materials, Korea Food Research Institute, Wanju 55365, Korea.
                [5 ]Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
                [6 ]Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
                [7 ]Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University, Collage of Medicine, Seoul 03080, Korea.
                [8 ]Department of Medicine, Pusan Paik Hospital, Inje University College of Medicine, Busan 47392, Korea.
                [9 ]Pulmonary Science and Critical Care Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul 04551, Korea.
                [10 ]Center for Respiratory Disease, College of Medicine, Yeungnam University, Daegu 42415, Korea.
                [11 ]Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang 25354, Korea.
                [12 ]Division of Vaccine Clinical Research Center for Vaccine Research, National Institute of Infectious Diseases, Cheongju 28160, Korea.
                [13 ]Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen 6500HB, Netherlands.
                Author notes
                Correspondence to Soohyun Kim. Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea. soohyun@ 123456konkuk.ac.kr

                Sinae Kim and Tam T. Nguyen contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-7767-5845
                https://orcid.org/0000-0002-0282-7760
                https://orcid.org/0000-0003-4504-1001
                https://orcid.org/0000-0002-3694-9715
                https://orcid.org/0000-0002-3694-9715
                https://orcid.org/0000-0002-6596-8253
                https://orcid.org/0000-0002-8029-7355
                https://orcid.org/0000-0003-1286-9611
                https://orcid.org/0000-0003-1972-1847
                https://orcid.org/0000-0002-4969-5443
                https://orcid.org/0000-0002-4158-6402
                https://orcid.org/0000-0002-9491-5740
                https://orcid.org/0000-0003-2421-6052
                https://orcid.org/0000-0002-0322-7935
                Article
                10.4110/in.2021.21.e38
                8733186
                35036025
                c63346e9-cd5a-41c4-aca6-a67fa10f2355
                Copyright © 2021. The Korean Association of Immunologists

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 December 2021
                : 19 December 2021
                : 19 December 2021
                Funding
                Funded by: National Research Foundation of Korea, CrossRef https://doi.org/10.13039/501100003725;
                Award ID: NRF-2021R1F1A1057397
                Funded by: Ministry of Science and ICT, South Korea, CrossRef https://doi.org/10.13039/501100014188;
                Award ID: E0210503-01
                Categories
                Review Article

                Immunology
                covid-19 omicron,sars-cov-2,spike (s) gene,mutation,receptor binding motif (rbm)
                Immunology
                covid-19 omicron, sars-cov-2, spike (s) gene, mutation, receptor binding motif (rbm)

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