DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20201957

COVID-19, the novel coronavirus 2019: current updates and the future

Pooja Singh, Shashank Kumar Srivastav, Akhil Mittal, Mansukhjeet Singh

Abstract


COVID-19 is a new strain that has not been previously identified in humans. It is large, enveloped, single-stranded RNA virus. The clinical features range from the common cold to more severe diseases i.e., MERS and SARS. Incubation period ranges between 1-12.5 days (median 5-6 days). As on 07 March, 2020 total confirmed cases are 1,01,927 with 3486 deaths in 93 countries/territories/areas. The various lab tests for COVID-19 virus are NAAT, serological testing, viral sequencing and viral culture. Many aspects of this virus is still not understood. The authors in this article describe studies to know the pathogenesis as well as immunological response with use of animal methods. Authors also discuss genetic engineering, evaluation of activation and inflammatory activity of myeloid cells during pathogenic human coronavirus, etc. that can help in prevention and treatment of COVID-19 in near future.


Keywords


Coronavirus, COVID-19, MERS-CoV, SARS-CoV

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References


Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. BioRxiv. 2020 Jan 1.

Paules CI, Marston HD, Fauci AS. Coronavirus infections—more than just the common cold. Jama. 2020 Feb 25;323(8):707-8.

Cohen J. Mining coronavirus genomes for clues to the outbreak’s origins. Science. 2020 Jan;31.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-13.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.

Holshue ML , Lindquist S L, Wiesman J B, Spitters CE, Wilkerson ST. First Case of 2019 Novel Corona virus in the UnitedStates. N Engl J Med. 2020.

Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res. 2006;117:17-37.

Lauber C, Goeman JJ, del Carmen Parquet M, Nga PT, Snijder EJ, Morita K, et al. The footprint of genome architecture in the largest genome expansion in RNA viruses. PLoS Pathogens. 2013 Jul;9(7).

Thiel V, Ivanov KA, Putics A, Hertzig T, Schelle B, Bayer S, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression. J General Virol. 2003 Sep 1;84(9):2305-15.

Subissi L, Imbert I, Ferron F, Collet A, Coutard B, Decroly E, et al. SARS-CoV ORF1b-encoded nonstructural proteins 12–16: replicative enzymes as antiviral targets. Antiviral Res. 2014 Jan 1;101:122-30.

Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE, Decroly E, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proceedings National Acad Sci. 2014 Sep 16;111(37):E3900-9.

Prentice E, McAuliffe J, Lu X, Subbarao K, Denison MR. Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins. J Virol. 2004;78(18):9977-86.

Hao W, Wojdyla JA, Zhao R, Han R, Das R, Zlatev I, et al. Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathogens. 2017 Jun 26;13(6):e1006474.

Ivanov KA, Thiel V, Dobbe JC, van der Meer Y, Snijder EJ, Ziebuhr J. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol. 2004 Jun 1;78(11):5619-32.

Adedeji AO, Lazarus H. Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase. mSphere. 2016 Oct 26;1(5):e00235-16.

World Health Organization. Laboratory testing for middle East respiratory syndrome coronavirus: interim guidance (revised), January 2018. World Health Organization; 2018.

Chen Y, Chan KH, Kang Y, Chen H, Luk HK, Poon RW, et al. A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus. Emerging Microbes Infect. 2015 Jan 1;4(1):1-5.

Corman V, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Eurosurveillance. 2012 Sep 1;17(39).

Corman V, Müller M, Costabel U, Timm J, Binger T, Meyer B, et al. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance. 2012 Dec 27;17(49).

Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infectious Dis. 2015 May 1;15(5):559-64.

Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Eurosurveillance. 2013 Sep 5;18(36):20574.

Saeidnia S, Abdollahi M. Are other fluorescent tags used instead of ethidium bromide safer? Daru 21(1):71

Drosten C, Seilmaier M, Corman VM, Hartmann W, Scheible G, Sack S, et al. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis. 2013 Sep 1;13(9):745-51.

Kapoor M, Pringle K, Kumar A, Dearth S, Liu L, Lovchik J, et al. Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States. Clinical Infectious Diseases. 2014 Dec 1;59(11):1511-8.

Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, de Wit E, et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio. 2014 May 1;5(2):e00884-14.

Hui DS, Azhar EI, Kim YJ, Memish ZA, M-d O, Zumla A. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis. 2018;18: e217-27.

Alfaraj SH, Al-Tawfiq JA, Altuwaijri TA, Alanazi M, Alzahrani N, Memish ZA. Middle East respiratory syndrome coronavirus transmission among health care workers: implication for infection control. Am J Infect Control. 2018;46(2):165-8.

Alsaad KO, Hajeer AH, Al Balwi M, Al Moaiqel M, Al Oudah N, Al Ajlan A, et al. Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection—clinicopathological and ultrastructural study. Histopathology. 2018;72:516-24.

Ng DL, Al Hosani F, Keating MK, Gerber SI, Jones TL, Metcalfe MG, et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am J Pathol. 2016;186:652-8.

Oh MD, Park WB, Choe PG, Choi SJ, Kim JI, Chae J, et al. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016 Sep 29;375(13):1303-5.

de Wit E, Prescott J, Baseler L, Bushmaker T, Thomas T, Lackemeyer MG, et al. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. PloS One. 2013;8(7).

Raj VS, Smits SL, Provacia LB, van den Brand JM, Wiersma L, Ouwendijk WJ, et al. Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus. J Virol. 2014;88:1834-8.

Coleman CM, Matthews KL, Goicochea L, Frieman MB. Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome corona- virus. J Gen Virol. 2014;95:408-12

Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar;495(7440):251-4.

Peck KM, Burch CL, Heise MT, Baric RS. Coronavirus host range expansion and Middle East respiratory syndrome coronavirus emergence: biochemical mechanisms and evolutionary perspectives. Annual Rev Virol. 2015 Nov 9;2:95-117.

Barlan A, Zhao J, Sarkar MK, Li K, McCray PB, Perlman S, et al. Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection. J Virol. 2014 May 1;88(9):4953-61.

Cockrell AS, Peck KM, Yount BL, Agnihothram SS, Scobey T, Curnes NR, et al. Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. J Virol. 2014;88:5195-9.

Peck KM, Cockrell AS, Yount BL, Scobey T, Baric RS, Heise MT. Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection. J Virol. 2015;89:4696-9.

Peck KM, Scobey T, Swanstrom J, Jensen KL, Burch CL, Baric RS, et al. Permissivity of dipeptidyl peptidase 4 orthologs to Middle East respiratory syndrome coronavirus is governed by glycosylation and other complex determinants. J Virol. 2017 Oct 1;91(19):e00534-17.

Van Doremalen N, Miazgowicz KL, Milne- Price S, Bushmaker T, Robertson S, Scott D, et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol.2014;88:9220-32.

Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Zhao J, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proceedings National Acad Sci. 2014 Apr 1;111(13):4970-5.

Agrawal AS, Garron T, Tao X, Peng BH, Wakamiya M, Chan TS, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol. 2015 Apr 1;89(7):3659-70.

Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, et al. Middle East Respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis. 213:712-22.

Zhao G, Jiang Y, Qiu H, Gao T, Zeng Y, Guo Y, et al. Multi-organ damage in human dipeptidyl peptidase 4 transgenic mice infected with Middle East respiratory syndrome-coronavirus. PLoS One. 2015;10:e0145561.

Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, et al. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanised mouse model of MERS- CoV infection. Proc Natl Acad Sci U S A. 2015;112:8738-43.

Klemann C, Wagner L, Stephan M, von Hörsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase‐4's (DPP4) entanglement in the immune system. Clini Experimental Immunol. 2016 Jul;185(1):1-21.

Li K, Wohlford-Lenane CL, Channappanavar R, Park JE, Earnest JT, Bair TB, et al. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proceedings of the National Acad Sci. 2017 Apr 11;114(15):E3119-28.

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Sci. 2013 Feb 15;339(6121):819-23.

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-guided human genome engineering via Cas9. Sci. 2013;339:823-6.

Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R. One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell. 2013; 154:1370-9.

Cockrell AS, Yount BL, Scobey T, Jensen K, Douglas M, Beall A, et al. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nat Microbiol. 2016;2:16226.

Douglas MG, Kocher JF, Scobey T, Baric RS, Cockrell AS. Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease. Virol. 2018;517:98-107.

Cockrell AS, Leist SR, Douglas MG, Baric RS. Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice. Mamm Genome. 2018;29:367-83.

Cockrell AS, Johnson JC, Moore IN, Liu DX, Bock KW, Douglas MG, et al. A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques. Sci Rep. 2018; 8:10727.

Chefer S, Seidel J, Cockrell AS, Yount B, Solomon J, Hagen KR, et al. The human sodium iodide symporter as a reporter gene for studying Middle East respiratory syndrome coronavirus pathogenesis. 2018;2018.

Leist SR, Baric RS. Giving the genes a shuffle: using natural variation to understand host genetic contributions to viral infections. Trends Genet.2018; 34:777-89.

Menachery VD, Gralinski LE, Mitchell HD, Dinnon KH, Leist SR, Yount BL, et al. Middle east respiratory syndrome coronavirus nonstructural protein 16 is necessary for interferon resistance and viral pathogenesis. mSphere. 2017 Dec 27;2(6):e00346-17.

Menachery VD, Mitchell HD, Cockrell AS, Gralinski LE, Yount BL, Graham RL, et al. MERS-CoV accessory ORFs play key role for infection and pathogenesis. MBio. 2017 Sep 6;8(4):e00665-17.

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9:eaal3653.

Huijbers IJ. Generating genetically modified mice: a decision guide. Methods Mol Biol. 2017;1642:1-19.

Scott GJ, Gruzdev A. (2019) Genome editing in mouse embryos with CRISPR/Cas9. Meth- ods Mol Biol. 2019;1960:23-40.

Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Zhao J, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proceedings National Acad Sci. 2014 Apr 1;111(13):4970-5.

Agrawal AS, Garron T, Tao X, Peng BH, Wakamiya M, Chan TS, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol. 2015 Apr 1;89(7):3659-70.

Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012 Nov 8;367(19):1814-20.

Cockrell AS, Yount BL, Scobey T, Jensen K, Douglas M, Beall A, et al. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nature Microb. 2016 Nov 28;2(2):1-1.

Li K, Wohlford-Lenane CL, Channappanavar R, Park JE, Earnest JT, Bair TB, et al. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proceedings National Acad Sci. 2017 Apr 11;114(15):E3119-28.

Roberts A, Deming D, Paddock CD, Cheng A, Yount B, Vogel L, et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS pathogens. 2007 Jan;3(1).

Day CW, Baric R, Cai SX, Frieman M, Kumaki Y, Morrey JD, et al. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. Virol. 2009 Dec 20;395(2):210-22.

Frieman M, Yount B, Agnihothram S, Page C, Donaldson E, Roberts A, et al. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J Virol. 2012 Jan 15;86(2):884-97.

Nicod C, Banaei-Esfahani A, Collins BC. Elucidation of host–pathogen protein–protein interactions to uncover mechanisms of host cell rewiring. Current Opinion Microbiol. 2017 Oct 1;39:7-15.

Wang YP, Lei QY. Metabolite sensing and signaling in cell metabolism. Signal Transduction Targeted Ther. 2018 Nov 9;3(1):1-9.

DeBerardinis RJ, Thompson CB. Cellular metabolism and disease: what do metabolic outliers teach us?. Cell. 2012 Mar 16;148(6):1132-44.

Sanchez EL, Lagunoff M. Viral activation of cellular metabolism. Virol. 2015 May 1;479:609-18.

Knoops K, Kikkert M, van den Worm SH, Zevenhoven-Dobbe JC, van der Meer Y, Koster AJ, Mommaas AM, Snijder EJ. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS biology. 2008 Sep;6(9):1957-74.

Knoops K, Swett-Tapia C, van den Worm SH, Te Velthuis AJ, Koster AJ, Mommaas AM, et al. Integrity of the early secretory pathway promotes, but is not required for, severe acute respiratory syndrome coronavirus RNA synthesis and virus-induced remodeling of endoplasmic reticulum membranes. J Virol. 2010 Jan 15;84(2):833-46.

Ulasli M, Verheije MH, de Haan CA, Reggiori F. Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus. Cellular Microbiol. 2010 Jun;12(6):844-61.

Wilde AH, Raj VS, Oudshoorn D, Bestebroer TM, van Nieuwkoop S, Limpens RW, et al. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. J General Virol. 2013 Aug;94(Pt 8):1749.

Nakayasu ES, Nicora CD, Sims AC, Burnum-Johnson KE, Kim YM, Kyle JE, et al. MPLEx: a robust and universal protocol for single-sample integrative proteomic, metabolomic, and lipidomic analyses. Msystems. 2016 Jun 28;1(3):e00043-16.

Burnum-Johnson KE, Kyle JE, Eisfeld AJ, Casey CP, Stratton KG, Gonzalez JF, et al. MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling. Analyst. 2017;142(3):442-8.

Folch J, Lees M, Stanley GS. A simple method for the isolation and purification of total lipides from animal tissues. J Biolo Chem. 1957 May 1;226(1):497-509.

Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nature Reviews Immunol. 2011 Nov;11(11):762-74.

Camp JV, Jonsson CB. A role for neutrophils in viral respiratory disease. Frontiers Immunol. 2017 May 12;8:550.

Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. MBio. 2018 Nov 7;9(5):e01753-18.

Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016 Feb 10;19(2):181-93.

Davidson S, Crotta S, McCabe TM, Wack A. Pathogenic potential of interferon αβ in acute influenza infection. Nature Communications. 2014 May 21;5(1):1-5.

Högner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, Walmrath HD, Bodner J, Gattenlöhner S, Lewe-Schlosser P, Matrosovich M. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS pathogens. 2013 Feb;9(2).

Fujikura D, Chiba S, Muramatsu D, Kazumata M, Nakayama Y, Kawai T, et al. Type-I interferon is critical for FasL expression on lung cells to determine the severity of influenza. PLoS One.2014;8(2):e55321.

Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell. 2011;146(6):980-91.

Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2013;289(21):2801-9.

Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015 Sep 5;386(9997):995-1007.

Khalid I, Alraddadi BM, Dairi Y, Khalid TJ, Kadri M, Alshukairi AN, et al. Acute management and long-term survival among subjects with severe Middle East respi- ratory syndrome coronavirus pneumonia and ARDS. Respir Care. 2016; 61(3):340-8.

Ng DL, Al Hosani F, Keating MK, Gerber SI, Jones TL, Metcalfe MG, et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, april 2014. Am J Pathol. 2016;186(3):652-8.

Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-72.

Cockrell AS, Johnson JC, Moore IN, Liu DX, Bock KW, Douglas MG, et al. A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques. Sci Rep. 2017;8(1):10727.

Hua X, Vijay R, Channappanavar R, Athmer J, Meyerholz DK, Pagedar N, et al. Nasal priming by a murine coronavirus provides protective immunity against lethal heterologous virus pneumonia. JCI Insight. 2018;3(11):99025.

Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, et al. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infecti Dis. 2016 Mar 1;213(5):712-22.

Menachery VD, Yount BL Jr, Debbink K, Agnihothram S, Gralinski LE, Plante JA, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med. 2005;21(12):1508-13.

Meyerholz DK, Lambertz AM, McCray PB Jr. Dipeptidyl peptidase 4 distribution in the human respiratory tract: implications for the Middle East respiratory syndrome. Am J Pathol. 2016;186(1):78-86.