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      The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade

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          Abstract

          In 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.

          Highlights

          • •

            The genomic sequence of 2019-nCoV indicates that the virus clusters with betacoronaviruses of lineage b.

          • •

            2019-nCoV S-protein sequence has a specific furin-like cleavage site absent in lineage b CoV including SARS-CoV sequences.

          • •

            The furin-like cleavage site in the S-protein of 2019-nCoV may have implications for the viral life cycle and pathogenicity.

          • •

            Campaigns to develop anti-2019-nCoV therapeutics should include the evaluation of furin inhibitors.

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          Qun Li, Xuhua Guan, Peng Wu … (2020)
          Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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            Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

            Yushun Wan, Jian Shang, Rachel Graham … (2020)
            The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 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.
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              Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

              Jasper Chan, Kin-Hang Kok, Zheng Zhu … (2020)
              ABSTRACT A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
              Article 0 comments Cited 1414 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                E. Decroly
                Journal
                Journal ID (nlm-ta): Antiviral Res
                Journal ID (iso-abbrev): Antiviral Res
                Title: Antiviral Research
                Publisher: Elsevier B.V.
                ISSN (Print): 0166-3542
                ISSN (Electronic): 1872-9096
                Publication date PMC-release: 10 February 2020
                Publication date (Print): April 2020
                Publication date (Electronic): 10 February 2020
                Volume: 176
                Page: 104742
                Affiliations
                [a ]Unité des Virus Émergents (UVE: Aix-Marseille Univ – IRD 190 – Inserm 1207 – IHU Méditerranée Infection), Marseille, France
                [b ]Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France
                [c ]Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM, Affiliated to the University of Montreal), 110 Pine Ave West, Montreal, QC, H2W1R7, Canada
                Author notes
                [∗ ]Corresponding author. etienne.decroly@ 123456afmb.univ-mrs.fr
                Article
                Publisher ID: S0166-3542(20)30052-8 Publisher ID: 104742
                DOI: 10.1016/j.antiviral.2020.104742
                PMC ID: 7114094
                PubMed ID: 32057769
                SO-VID: 0d98a1d0-aa0d-47ff-b9fa-c711bdd5df95
                Copyright © © 2020 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 3 February 2020
                Date revision received : 7 February 2020
                Date accepted : 8 February 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: 2019-ncov,sars-cov,spike protein,maturation protease,furin,antivirals
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: 2019-ncov, sars-cov, spike protein, maturation protease, furin, antivirals

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