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      Repurposing Drugs, Ongoing Vaccine, and New Therapeutic Development Initiatives Against COVID-19

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          Abstract

          As the COVID-19 is still growing throughout the globe, a thorough investigation into the specific immunopathology of SARS-CoV-2, its interaction with the host immune system and pathogen evasion mechanism may provide a clear picture of how the pathogen can breach the host immune defenses in elderly patients and patients with comorbid conditions. Such studies will also reveal the underlying mechanism of how children and young patients can withstand the disease better. The study of the immune defense mechanisms and the prolonged immune memory from patients population with convalescent plasma may help in designing a suitable vaccine candidate not only for the current outbreak but also for similar outbreaks in the future. The vital drug candidates, which are being tested as potential vaccines or therapeutics against COVID-19, include live attenuated vaccine, inactivated or killed vaccine, subunit vaccine, antibodies, interferon treatment, repurposing existing drugs, and nucleic acid-based vaccines. Several organizations around the world have fast-tracked the development of a COVID-19 vaccine, and some drugs already went to phase III of clinical trials. Hence, here, we have tried to take a quick glimpse of the development stages of vaccines or therapeutic approaches to treat this deadly disease.

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

          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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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              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.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                19 August 2020
                2020
                19 August 2020
                : 11
                : 1258
                Affiliations
                [1] 1 Department of Biotechnology, School of Life Science & Biotechnology, Adamas University , Kolkata, India
                [2] 2 Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital , Chuncheon-si, South Korea
                Author notes

                Edited by: Rosario Pignatello, University of Catania, Italy

                Reviewed by: Mariusz Skwarczynski, The University of Queensland, Australia; Lucia Gozzo, Gaspare Rodolico Hospital, Italy

                This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work

                Article
                10.3389/fphar.2020.01258
                7466451
                32973505
                126b3021-5d56-4e17-a829-08fca4809280
                Copyright © 2020 Saha, Sharma, Singh, Samanta, Bhakta, Mandal, Bhattacharya, Lee and Chakraborty

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 May 2020
                : 30 July 2020
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 234, Pages: 33, Words: 17596
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                coronavirus,vaccine development,sars-cov-2,repurposed drug,antiviral treatment,covid-19

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