1
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Pan‐coronavirus fusion inhibitors to combat COVID‐19 and other emerging coronavirus infectious diseases

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative agent of the currently ongoing coronavirus disease 2019 (COVID‐19) pandemic, has posed a serious threat to global public health. Recently, several SARS‐CoV‐2 variants of concern (VOCs) have emerged and caused numerous cases of reinfection in convalescent COVID‐19 patients, as well as breakthrough infections in vaccinated individuals. This calls for the development of broad‐spectrum antiviral drugs to combat SARS‐CoV‐2 and its VOCs. Pan‐coronavirus fusion inhibitors, targeting the conserved heptad repeat 1 (HR1) in spike protein S2 subunit, can broadly and potently inhibit infection of SARS‐CoV‐2 and its variants, as well as other human coronaviruses. In this review, we summarized the most recent development of pan‐coronavirus fusion inhibitors, such as EK1, EK1C4, and EKL1C, and highlighted their potential application in combating current COVID‐19 infection and reinfection, as well as future emerging coronavirus infectious diseases.

          Related collections

          Most cited references53

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Characteristics of SARS-CoV-2 and COVID-19

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              SARS-CoV-2 variants, spike mutations and immune escape

              Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.
                Bookmark

                Author and article information

                Contributors
                sxia15@fudan.edu.cn
                shibojiang@fudan.edu.cn
                Journal
                J Med Virol
                J Med Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                22 September 2022
                22 September 2022
                : 10.1002/jmv.28143
                Affiliations
                [ 1 ] Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity Fudan University Shanghai China
                Author notes
                [*] [* ] Correspondence Shibo Jiang and Shuai Xia, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.

                Email: shibojiang@ 123456fudan.edu.cn and

                sxia15@ 123456fudan.edu.cn

                Author information
                http://orcid.org/0000-0001-5524-3542
                http://orcid.org/0000-0002-2255-0391
                http://orcid.org/0000-0001-8283-7135
                Article
                JMV28143
                10.1002/jmv.28143
                9539121
                36098460
                22140d83-bf09-479a-bc94-eaddfcca5e46
                © 2022 Wiley Periodicals LLC.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 08 September 2022
                : 23 August 2022
                : 09 September 2022
                Page count
                Figures: 1, Tables: 2, Pages: 8, Words: 4819
                Funding
                Funded by: Shanghai Municipal Science and Technology Major Project
                Funded by: National Key Research and Development Program of China
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Microbiology & Virology
                coronavirus,covid‐19,ek1,fusion inhibitor,heptad repeat 1,lipopeptide
                Microbiology & Virology
                coronavirus, covid‐19, ek1, fusion inhibitor, heptad repeat 1, lipopeptide

                Comments

                Comment on this article