Coronavirus

Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are as yet no vaccines or antiviral drugs to prevent or treat human coronavirus infections.

Origin

The most recent common ancestor (MRCA) of all coronaviruses is estimated to have existed as recently as 8000 BCE, although some models place the common ancestor as far back as 55 million years or more, implying long term coevolution with bat and avian species.[63] The most recent common ancestor of the alphacoronavirus line has been placed at about 2400 BCE, of the betacoronavirus line at 3300 BCE, of the gammacoronavirus line at 2800 BCE, and of the deltacoronavirus line at about 3000 BCE. Bats and birds, as warm-blooded flying vertebrates, are an ideal natural reservoir for the coronavirus gene pool (with bats the reservoir for alphacoronaviruses and betacoronavirus – and birds the reservoir for gammacoronaviruses and deltacoronaviruses). The large number and global range of bat and avian species that host viruses has enabled extensive evolution and dissemination of coronaviruses.[64]

Many human coronaviruses have their origin in bats.[65] The human coronavirus NL63 shared a common ancestor with a bat coronavirus (ARCoV.2) between 1190 and 1449 CE.[66] The human coronavirus 229E shared a common ancestor with a bat coronavirus (GhanaGrp1 Bt CoV) between 1686 and 1800 CE.[67] More recently, alpaca coronavirus and human coronavirus 229E diverged sometime before 1960.[68] MERS-CoV emerged in humans from bats through the intermediate host of camels.[69] MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.[70] The most closely related bat coronavirus and SARS-CoV diverged in 1986.[71] A possible path of evolution of SARS coronavirus and keen bat coronaviruses is that SARS-related coronaviruses coevolved in bats for a long time. The ancestors of SARS-CoV first infected leaf-nose bats of the genus Hipposideridae; subsequently, they spread to horseshoe bats in the species Rhinolophidae, then to Asian palm civets, and finally to humans.[72][73]

Unlike other betacoronaviruses, bovine coronavirus of the species Betacoronavirus 1 and subgenus Embecovirus is thought to have originated in rodents and not in bats.[65][74] In the 1790s, equine coronavirus diverged from the bovine coronavirus after a cross-species jump.[75] Later in the 1890s, human coronavirus OC43 diverged from bovine coronavirus after another cross-species spillover event.[76][75] It is speculated that the flu pandemic of 1890 may have been caused by this spillover event, and not by the influenza virus, because of the related timing, neurological symptoms, and unknown causative agent of the pandemic.[77] Besides causing respiratory infections, human coronavirus OC43 is also suspected of playing a role in neurological diseases.[78] In the 1950s, the human coronavirus OC43 began to diverge into its present genotypes.[79] Phylogentically, mouse hepatitis virus (Murine coronavirus), which infects the mouse's liver and central nervous system,[80] is related to human coronavirus OC43 and bovine coronavirus. Human coronavirus HKU1, like the aforementioned viruses, also has its origins in rodents.[65]

History

Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus (IBV).[14] Arthur Schalk and M.C. Hawn described in 1931 a new respiratory infection of chickens in North Dakota. The infection of new-born chicks was characterized by gasping and listlessness. The chicks' mortality rate was 40–90%.[15] Fred Beaudette and Charles Hudson six years later successfully isolated and cultivated the infectious bronchitis virus which caused the disease.[16] In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated.[17] It was not realized at the time that these three different viruses were related.[18]

Human coronaviruses were discovered in the 1960s.[19][20] They were isolated using two different methods in the United Kingdom and the United States.[21] E.C. Kendall, Malcom Byone, and David Tyrrell working at the Common Cold Unit of the British Medical Research Council in 1960 isolated from a boy a novel common cold virus B814.[22][23][24] The virus was not able to be cultivated using standard techniques which had successfully cultivated rhinoviruses, adenoviruses and other known common cold viruses. In 1965, Tyrrell and Byone successfully cultivated the novel virus by serially passing it through organ culture of human embryonic trachea.[25] The new cultivating method was introduced to the lab by Bertil Hoorn.[26] The isolated virus when intranasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope.[22][27] Around the same time, Dorothy Hamre[28] and John Procknow at the University of Chicago isolated a novel cold virus 229E from medical students, which they grew in kidney tissue culture. The novel virus 229E, like the virus strain B814, when inoculated into volunteers caused a cold and was inactivated by ether.[29]

Transmission electron micrograph of organ cultured coronavirus OC43

The two novel strains B814 and 229E were subsequently imaged by electron microscopy in 1967 by Scottish virologist June Almeida at St. Thomas Hospital in London.[30][31] Almeida through electron microscopy was able to show that B814 and 229E were morphologically related by their distinctive club-like spikes. Not only were they related with each other, but they were morphologically related to infectious bronchitis virus (IBV).[32] A research group at the National Institute of Health the same year was able to isolate another member of this new group of viruses using organ culture and named the virus strain OC43 (OC for organ culture).[33] Like B814, 229E, and IBV, the novel cold virus OC43 had distinctive club-like spikes when observed with the electron microscope.[34][35]

The IBV-like novel cold viruses were soon shown to be also morphologically related to the mouse hepatitis virus.[17] This new group of IBV-like viruses came to be known as coronaviruses after their distinctive morphological appearance.[9] Human coronavirus 229E and human coronavirus OC43 continued to be studied in subsequent decades.[36][37] The coronavirus strain B814 was lost. It is not known which present human coronavirus it was.[38] Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HCoV HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019.[39][40] There have also been a large number of animal coronaviruses identified since the 1960s.[5]