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      The Role of Lipid Metabolism in COVID-19 Virus Infection and as a Drug Target

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          Abstract

          The current Coronavirus disease 2019 or COVID-19 pandemic has infected over two million people and resulted in the death of over one hundred thousand people at the time of writing this review. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though multiple vaccines and treatments are under development so far, the disease is only slowing down under extreme social distancing measures that are difficult to maintain. SARS-COV-2 is an enveloped virus that is surrounded by a lipid bilayer. Lipids are fundamental cell components that play various biological roles ranging from being a structural building block to a signaling molecule as well as a central energy store. The role lipids play in viral infection involves the fusion of the viral membrane to the host cell, viral replication, and viral endocytosis and exocytosis. Since lipids play a crucial function in the viral life cycle, we asked whether drugs targeting lipid metabolism, such as statins, can be utilized against SARS-CoV-2 and other viruses. In this review, we discuss the role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle.

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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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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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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
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                17 May 2020
                May 2020
                : 21
                : 10
                : 3544
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, 15462 Dasman, Kuwait; mohamed.abufarha@ 123456dasmaninstitute.org
                [2 ]Department of Genetic and Bioinformatics, Dasman Diabetes Institute, 15462 Dasman, Kuwait; alphonse.thangavel@ 123456dasmaninstitute.org
                [3 ]Pharmacology and Therapeutics Department, Faculty of Pharmacy, Kuwait University, 13110 Kuwait City, Kuwait; mohammad.qaddoumi@ 123456dasmaninstitute.org
                [4 ]Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 11633, Saudi Arabia; amhashem@ 123456kau.edu.sa
                [5 ]Vaccines and Immunotherapy Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 80205, Saudi Arabia
                Author notes
                [* ]Correspondence: jehad.abubakr@ 123456dasmaninstitute.org (J.A.); fahd.almulla@ 123456dasmaninstitute.org (F.A.-M.); Tel.: +965-2224-2999 (ext. 3563) (J.A.); +965-2224-2999 (ext. 2211) (F.A.-M.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-8357-1252
                https://orcid.org/0000-0001-5409-3829
                Article
                ijms-21-03544
                10.3390/ijms21103544
                7278986
                32429572
                91c198d9-cc59-49c6-b744-e03f3f1e24d3
                © 2020 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
                : 21 April 2020
                : 08 May 2020
                Categories
                Review

                Molecular biology
                coronavirus,covid-19,sars-cov-2,lipid metabolism,sphingolipid,endocytosis
                Molecular biology
                coronavirus, covid-19, sars-cov-2, lipid metabolism, sphingolipid, endocytosis

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