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      Exploration of antigenic determinants in spike glycoprotein of SARS-CoV2 and identification of five salient potential epitopes

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          Abstract

          Emerging pathogens have been an eternal threat to mankind. In a series of pandemics caused by notorious coronaviruses, a newly emerged SARS-CoV2 virus is creating panic among the world population. The unavailability of reliable theranostics insists the exploration of antigenic determinants in spike glycoprotein of SARS-CoV2. The four novel inserts (‘ 70VSGTNGT 76’, ‘ 150KSWM 153’, 247SYLTPG 252 and 674QTQTNSPRR 682) in SARS-CoV2 spike protein were unraveled via multiple sequence alignment of spike proteins of SARS-CoV2, SARS-CoV, and MERS-CoV. The three-dimension (3D) modeling of the spike protein of the SARS-CoV2 and their interaction with the ACE2 receptor was delineated with the help of SWISS-MODEL and 3DLigandSite web servers. The predicted 3D model of SARS-CoV2 was further verified by SAVES, RAMPAGE, and ProSA-web tools. The potential B-cell immunogenic epitopes of SARS-CoV2 were predicted out by using various software viz. IEDB B-cell epitopes prediction tool, BepiPred linear epitope prediction tool, Emini Surface Accessibility Prediction tool, and Kolaskar-Tongaonkar antigenicity web tool. The five epitopes ( i.e. ‘ 71SGTNGTKRFDN 81, 247SYLTPG 252, 634RVYST 638, 675QTQTNSPRRARSV 687, and 1054QSAPH 1058) were selected as potent antigenic determinants. The quantum of information generated by this study will prove beneficial for the development of effective therapeutics, diagnostics, and multi-epitopic vaccines to combat this ongoing menace.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

              Renhong Yan, Yuanyuan Zhang, Yaning Li … (2020)
              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
              Article 0 comments Cited 2528 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ritu Varshney:
                ORCID: https://orcid.org/0000-0002-2290-6263
                rituvarshney.2009@gmail.com
                Ramadevi Nimmanapalli:
                ORCID: https://orcid.org/0000-0003-3827-6603
                ramadevi.nimmanapalli@gmail.com
                Journal
                Journal ID (nlm-ta): Virusdisease
                Journal ID (iso-abbrev): Virusdisease
                Title: VirusDisease
                Publisher: Springer India (New Delhi )
                ISSN (Print): 2347-3584
                ISSN (Electronic): 2347-3517
                Publication date (Electronic): 7 September 2021
                Pages: 1-10
                Affiliations
                [1 ]GRID grid.417990.2, ISNI 0000 0000 9070 5290, ICAR-Indian Veterinary Research Institute Izatnagar, ; Bareilly, Uttar Pradesh 243122 India
                [2 ]GRID grid.411507.6, ISNI 0000 0001 2287 8816, Department of Veterinary Microbiology, Faculty of Veterinary and Animal Sciences, IAS, RGSC, , Banaras Hindu University, ; Mirzapur, Uttar Pradesh 231001 India
                [3 ]GRID grid.448717.9, ISNI 0000 0004 7407 0386, Department of Animal Science, , Kazi Nazrul University, ; Asansol, West Bengal 713340 India
                [4 ]GRID grid.418821.6, Department of Veterinary Medicine, , Nanaji Deshmukh Veterinary Science University, ; Jabalpur, Madhya Pradesh 482001 India
                [5 ]GRID grid.462384.f, ISNI 0000 0004 1772 7433, Department of Biological Engineering, , Indian Institute of Technology Gandhinagar, ; Palaj, Gujarat 382355 India
                Author information
                https://orcid.org/0000-0001-7840-7159
                http://orcid.org/0000-0002-2658-2219
                https://orcid.org/0000-0002-2671-6715
                https://orcid.org/0000-0001-9536-4760
                https://orcid.org/0000-0001-6627-8126
                https://orcid.org/0000-0002-6481-608X
                https://orcid.org/0000-0001-6772-1994
                https://orcid.org/0000-0002-5978-2014
                https://orcid.org/0000-0002-2290-6263
                https://orcid.org/0000-0003-3827-6603
                Article
                Publisher ID: 737
                DOI: 10.1007/s13337-021-00737-9
                PMC ID: 8422955
                SO-VID: 396fd898-593a-45d3-83e1-7f1dbce4b1f2
                Copyright © © Indian Virological Society 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 5 March 2021
                Date accepted : 7 August 2021
                Categories
                Subject: Short Communication

                Keywords: sars-cov2,spike protein,ace2 receptor,vaccines,epitopes
                Data availability:
                Keywords: sars-cov2, spike protein, ace2 receptor, vaccines, epitopes

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