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      COVID-19: Characteristics and Therapeutics

      review-article
      , *
      Cells
      MDPI
      COVID-19, SARS-CoV-2, coronavirus, pandemic, vaccine, therapeutics, epidemiology, spike protein

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          Abstract

          Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

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          Most cited references195

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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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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                21 January 2021
                February 2021
                : 10
                : 2
                : 206
                Affiliations
                Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, 8000 Utopia Parkway, Queens, NY 11439, USA; rameswari.chilamakuri19@ 123456my.stjohns.edu
                Author notes
                [* ]Correspondence: agarwals@ 123456stjohns.edu ; Tel.: +1-718-990-3286
                Author information
                https://orcid.org/0000-0001-9758-6746
                Article
                cells-10-00206
                10.3390/cells10020206
                7909801
                33494237
                1c7ad501-a6ed-483c-a71b-fc07a6a58b61
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 November 2020
                : 18 January 2021
                Categories
                Review

                covid-19,sars-cov-2,coronavirus,pandemic,vaccine,therapeutics,epidemiology,spike protein

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