Issue link: https://wardsworld.wardsci.com/i/1304290
Coronavirus (continued) + ward ' s science The viral genome is coated or complexed with nucleocapsid (N) proteins to form a helical nucleocapsid. In addition to the genes that code for the structural proteins that are the building blocks of the coronavirus particle (S, HE, E, M, and N proteins), the genome codes for 16 or more additional genes that func- tion in replication, manipulating the activities of the host cell; these activities include slowing down the cell's protein syn- thesis machinery, allowing the adaptation to different tissues or cell types of hosts, and evading an affected body's immune system. Coronavirus research Before the SARS pandemic in 2003, coronaviruses were not known to be highly pathogenic in humans. In particular, the HCoV 229E and OC43 strains were exclusively studied by researchers because the strains could be adapted to growth in laboratory tissue cultures, thereby facilitating experimental investigations. Mouse hepatitis virus (MHV) is one of the most studied coronaviruses. MHV was discovered in 1950 when a labora- tory breeding stock of white mice died from fatal hepatitis. MHV caused the hepatitis, and researchers later determined that MHV could be isolated from paralyzed white mice suffer- ing from encephalomyelitis [the destruction of myelin (a fatty substance that forms a sheath around certain nerve fibers) as a result of inflammation in the brain and spinal cord, which can be triggered by viral infections]. Subsequently, mice were used as a model to study fundamental questions about human hepatitis and multiple sclerosis (a demyelinating disease of the nervous system). In particular, scientists were interested in whether there were genetic factors in multiple sclerosis associated with clearing viral infections and what role the im- mune system played in causing the pathogenesis observed in multiple sclerosis. Other pre-SARS research focused on coronavirus infections having veterinary and economic importance. Various respirato- ry and gastrointestinal diseases of pigs, cattle, horses, chickens, turkeys, dogs, and cats caused by coronavirus infections were studied. For example, porcine transmissible gastroenteritis resulted in mortalities approaching 100% in newborn pigs, but there also were strains of porcine coronaviruses that caused mild respiratory illness with no gastrointestinal symptoms. In addition, symptoms of winter dysentery in dairy cattle included bloody diarrhea, respiratory illness, and low milk yields during the winter months, and bovine shipping fever (pneumonia) was noted in feedlot cattle (raised for beef ). Coronavirus infec- tions were also reported in other species of animals, including ferrets, rabbits, guinea pigs, and rats. Since the onset of the SARS pandemic in 2003, scientific investigators sought to identify the zoonotic reservoir or source of SARS-CoV-1, and its transmission to humans. For example, researchers used serological surveillance methodologies to screen for antibodies against coronaviruses present in blood samples of domestic and wild mammals and birds (including animals on farms and those sold in live markets), leading to the discovery of a significant number of novel coronaviruses. More- over, scientists isolated dozens of coronaviruses from a wide variety of bat species (order Chiroptera) in Asia, Africa, Europe, and America. In addition, the coronavirus that causes MERS was detected in dromedary camels. In 2019, coronaviruses were found in the lung samples of two dead Malayan pangolins (order Pholidota) in Guangdong province in China. Pangolins are an endangered species and are the most illegally trafficked mammal in the world. In China, they are used as a food source, and their scales are used in tra- ditional Chinese medicine. The two aforementioned pangolins had frothy liquid in their lungs and pulmonary fibrosis (a pa- thology also observed in COVID-19 patients). Genetic analysis determined that the coronaviruses from these pangolins were 91% and 90.5% identical to SARS-CoV-2, which was the virus responsible for the COVID-19 outbreak that began in Wuhan, China, toward the end of 2019. These results suggest that SARS-CoV-2 may have originated in pangolins, which acted as intermediate hosts of the virus. However, other possible animal sources of SARS-CoV-2 include bats as primary hosts (reser- voirs) of the virus. Coronavirus classification/taxonomy Coronaviruses are classified in the family Coronaviridae and the subfamily Orthocoronavirinae. The subfamily is divided into four genera, based on differences in protein sequences: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (Fig. 3). Alphacoronaviruses and betacorona- viruses circulate in mammals, including bats, especially causing respiratory illnesses in humans and gastroenteritis in animals. These viruses also pose a heavy burden on livestock. Deltacoro- naviruses mostly infect birds, whereas gammacoronaviruses infect birds and mammals. Seven coronaviruses are known to cause infections in humans. Four of these coronaviruses cause mild respiratory illness: HCoV 229E, HCoV OC43, HCoV NL63, and HCoV HKU1 (Table 1). The remaining three coronaviruses are emergent viruses that cause severe respiratory distress/pneumonia and even death: SARS-CoV-1, MERS-CoV, and SARS-CoV-2 (Table 2). All of the human coronavirus genomes have been sequenced. Based on a comprehensive comparison to the coronavirus genome sequences available in genomic databases, all human coronaviruses have animal origins.