pathogens Review Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks Hossam M. Ashour 1,2,*, Walid F. Elkhatib 3,4 , Md. Masudur Rahman 5 and Hatem A. Elshabrawy 6,* 1 Department of Biological Sciences, College of Arts and Sciences, University of South Florida St. Petersburg, St. Petersburg, FL 33701, USA 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt 3 Department of Microbiology and Immunology, School of Pharmacy & Pharmaceutical Industries, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo 11829, Egypt; [email protected] 4 Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia, Cairo 11566, Egypt 5 Department of Pathology, Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet 3100, Bangladesh; [email protected] 6 Department of Molecular and Cellular Biology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA * Correspondence: [email protected] (H.M.A.); [email protected] (H.A.E.) Received: 5 February 2020; Accepted: 2 March 2020; Published: 4 March 2020 Abstract: Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat. Keywords: 2019-nCoV; SARS-CoV-2; SARS; MERS; COVID-19 1. Introduction Coronaviruses (CoVs) were discovered in the 1960s and they were classified under family Coronaviridae, which is the largest family within the order Nidovirales (Figure1)[ 1]. Family Coronaviridae encompasses two subfamilies: subfamily Orthocoronavirinae and subfamily Torovirinae (Figure1)[ 1]. Subfamily Orthocoronavirinae includes four genera: alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus (Figure1)[ 1]. CoVs are typically harbored in mammals and birds and are common in camels, cattle, cats, bats, and other animals [2]. Alpha and betacoronaviruses circulate in mammals, including bats (Figure1)[ 2]. Gammacoronaviruses mostly infect avian species Pathogens 2020, 9, 186; doi:10.3390/pathogens9030186 www.mdpi.com/journal/pathogens Pathogens 2020, 9, 186 2 of 15 Pathogens 2020, 9, 186 2 of 15 infect avian species and a few mammalian species, whereas deltacoronaviruses infect birds and mammals (Figure 1) [2]. Animal CoVs are known to cause important diseases in animals and could beand responsible a few mammalian for economic species, losses whereas in domestic deltacoronaviruses animals or birds infect [3–5]. birds These and mammals animal CoVs (Figure include1)[ 2 ]. avianAnimal infectious CoVs are bronchitis known to virus cause (IBV), important transmissible diseases gastroenteritis in animals and virus could (TGEV), be responsible porcine for epidemic economic diarrhealosses in virus domestic (PEDV), animals and or birdsmore [3recently,–5]. These sw animaline acute CoVs diarrhea include aviansyndrome-CoV infectious bronchitis(SADS-CoV). virus Although(IBV), transmissible rare, animal gastroenteritis CoVs have the virus ability (TGEV), to infect porcine humans epidemic and diarrhea could further virus (PEDV), spread andthrough more human-to-humanrecently, swine acute transmission diarrhea [6,7]. syndrome-CoV (SADS-CoV). Although rare, animal CoVs have the ability to infect humans and could further spread through human-to-human transmission [6,7]. Figure 1. Classification of different types of coronaviruses within the family Coronaviridae, subfamily Figure 1. Classification of different types of coronaviruses within the family Coronaviridae, subfamily Orthocoronavirinae, and the respective genera: alpha-, beta-, gamma-, and deltacoronaviruses. The Orthocoronavirinae, and the respective genera: alpha-, beta-, gamma-, and deltacoronaviruses. The SARS-CoV-2 is classified as a betacoronavirus. SARS-CoV-2 is classified as a betacoronavirus. The first discovered CoVs were IBV that causes respiratory disease in chickens and the human CoVs,The human first discovered CoV-229E (HCoV-229E)CoVs were IBV and that human causes CoV-OC43 respiratory (HCoV-OC43), disease in chickens which cause and the commonhuman CoVs,cold inhuman humans CoV-229E [8,9]. Since (HCoV-229E) the emergence and of HCoV-229Ehuman CoV-OC43 and HCoV-OC43, (HCoV-OC43), several which other HCoVscause werethe commondiscovered, cold such in humans as Severe [8,9]. Acute Since Respiratory the emerge Syndrome-CoVnce of HCoV-229E (SARS-CoV) and HCoV-OC43, in 2002, HCoV-NL63several other in HCoVs2004, HCoV-HKU1 were discovered, in 2005, such Middle as Severe East Respiratory Acute Respiratory Syndrome-CoV Syndrome-CoV (MERS-CoV) (SARS-CoV) in 2012 [10 ].in Starting 2002, HCoV-NL63December 2019, in 2004, there HCoV-HKU1 were reports in of 2005, patients Middle presenting East Respiratory with severe Syndrome-CoV viral pneumonia (MERS-CoV) in the city in of 2012Wuhan, [10]. ChinaStarting [11 ].December Sequencing 2019, of thethere virus were from reports these of patients patients has presenting identified awith novel severe CoV asviral the pneumoniacausative agentin the of city this respiratoryof Wuhan, diseaseChina [11]. [11]. TheSequencing 2019 novel of CoVthe virus virus from (2019-nCoV) these patients was recently has identifiednamed SARS-CoV-2 a novel CoV by as the the World causative Health agent Organization of this respiratory (WHO). Thedisease disease [11]. caused The 2019 by SARS-CoV-2novel CoV virushas been(2019-nCoV) named COVID-19. was recently Prior named to 2002, SARS-CoV-2 CoVs were by treated the World as nuisances Health Organization but never as serious (WHO). viruses. The diseaseThings caused changed by afterSARS-CoV-2 the emergence has been of SARS-CoV,named COVID-19. which causedPrior to serious 2002, CoVs illnesses were and treated deaths as in nuisances2002–2003 but [12 ].never Unlike as allserious human viruses. CoVs thatThings cause changed mild respiratory after the emergence symptoms, SARS-CoV,of SARS-CoV, MERS-CoV, which causedand SARS-CoV-2 serious illnesses are associated and deaths with in serious 2002–2003 respiratory [12]. Unlike diseases all [human12,13]. SinceCoVs itsthat emergence, cause mild the respiratorySARS-CoV-2 symptoms, has drawn well-deservedSARS-CoV, MERS-CoV, attention from and the SARS-CoV-2 world. Efforts are are associated underway inwith an attemptserious to respiratorycontrol this diseases new CoV [12,13]. outbreak. Since its emergence, the SARS-CoV-2 has drawn well-deserved attention from the world. Efforts are underway in an attempt to control this new CoV outbreak. 2. Coronavirus Structure 2. Coronavirus Structure CoVs, including the newly discovered SARS-CoV-2, are spherical positive single-stranded RNA virusesCoVs, that including are characterized the newly by discovered spike proteins SARS-CoV-2 projecting, are from spherical the virion positive surface single-stranded [14,15]. The spherical RNA virusesmorphology that are of thecharacterized viral particle by together spike proteins with the spikeprojecting projections from ledthe tovirion the name surface coronavirus [14,15]. The from sphericalthe Latin morphology word corona of meaning the viral crown, particle due totogether the appearance with the of spike the virus projections as a royal led crown to the under name the coronaviruselectron microscope from the Latin [14,15 word]. CoVs corona are enveloped meaning crow virusesn, due (envelope to the appearance is a lipid bilayer of the derivedvirus as froma royal the crownhost cell under membrane) the electron with microscope the viral structure [14,15]. CoVs formed are primarily enveloped of structuralviruses (envelope proteins is such a lipid as spikebilayer (S), derivedmembrane from (M), the envelopehost cell membrane) (E), and nucleocapsid with the viral (N) structure proteins, andformed hemagglutinin-esterase primarily of structural (HE) proteins protein suchin some as spike betacoronaviruses (S), membrane [(M),16]. envelope The S, M, (E), and and E proteinsnucleocapsid are all (N) embedded proteins, inand the hemagglutinin- viral envelope; Pathogens 2020, 9, 186 3 of 15 however, N protein interacts with the viral RNA and is located in the core of the viral particle, forming the nucleocapsid [16]. The S protein is a heavily glycosylated protein that forms homotrimeric spikes on the surface of the viral particle and