In the mid-sixties of the previous century, the first two human coronaviruses (HCoV) were identified: HCoV-229E and HCoV-OC43. These two human coronaviruses were studied extensively from approximately 1965 to the mid-1980s. HCoV-229E is a member of the group I coronaviruses, and HCoV-OC43 is a member of group II. Besides the human coronaviruses, there are several group I and group II animal coronaviruses that infect cattle, pigs, cats, dogs, mice, and other animals. There is one additional branch, the group III coronaviruses, which are found exclusively in birds.
By infecting healthy volunteers, researchers learned that infection with HCoV-229E or HCoV-OC43 results in a common cold, and since then, HCoVs have been considered to be relatively harmless respiratory pathogens. This image was roughly disturbed when severe acute respiratory syndrome (SARS)-CoV was introduced into the human population in the winter of 2002 to 2003 in China. SARS-CoV causes a severe respiratory illness with high morbidity and mortality. The virus originated from a wild-animal reservoir, most likely bats, and was transmitted to humans via infected civet cats. The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is not currently circulating in humans. However, the SARS outbreak brought coronaviruses back into the limelight, and a renewed interest in this virus family resulted in the identification of two more human coronaviruses. HCoV-NL63, a novel member of group I, was discovered in a child with bronchiolitis in The Netherlands. HCoV-HKU1, a novel group II virus from an adult with chronic pulmonary disease in Hong Kong, was described in 2005.
The renewed interest in coronaviruses since the outbreak of SARS-CoV has revealed that at least four human coronaviruses circulate worldwide, generally causing relatively mild respiratory symptoms. However, in young children, immunocompromised patients, or otherwise-weakened persons, these viruses can cause more-serious respiratory tract disease that requires hospitalization.
The ACE2 molecule, which is used as a receptor by HCoV-NL63 and SARS-CoV, has recently been associated with respiratory disease. The fact that ACE2 is also involved in protection against lung damage is intriguing and suggests opportunities to treat complications during respiratory tract infections. The fact that SARS-CoV and HCoV-NL63 use the same receptor, while their pathogenicities and disease courses are utterly different, calls for detailed comparisons of the immune responses, inflammation processes, and in vivo replication characteristics of these two viruses.
The identification and characterization of novel respiratory viruses is of obvious clinical importance. Diagnostics can be improved, and new therapies can be developed. An antiviral strategy that would target all human coronaviruses, e.g., broad-spectrum inhibitors of the Mpro enzymes, is promising. For HCoV-NL63, several compounds that efficiently inhibit distinct steps of the viral replication cycle have been described. A short interfering RNA (siRNA) targeting the S gene of HCoV-NL63 is one of these potent inhibitors. Inhalation of a cocktail of siRNAs targeting all the different coronaviruses or perhaps all respiratory viruses may be an effective and simple therapy to block viral replication in the lungs.
Besides the above five human coronaviruses: HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63 and HCoV-HKU1, other novel human coronaviruses have also been discovered in recent years. A novel human coronavirus, hCoV-EMC, has recently emerged in the Middle East region. The virus has caused severe acute respiratory infection (SARI) in at least nine patients to date. Latest reports from the World Health Organization (WHO) suggest that infections have occurred since April 2012, as hCoV-EMC was found retrospectively in two patients from a group of 11 epidemiologically linked cases of SARI in Jordan, eight of whom were healthcare workers. And in September 2012, another novel human coronavirus - novel coronavirus 2012 was found. The case is a previously healthy, 49 year-old male Qatari national that presented with symptoms on 3 September 2012 with travel history to Saudi Arabia prior to onset of illness. On 7 September he was admitted to an intensive care unit (ICU) in Doha, Qatar. On 11 September, he was transferred to the UK by air ambulance from Qatar. The Health Protection Agency of the UK (HPA) conducted laboratory testing and has confirmed the presence of a novel coronavirus.
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