Coronavirus

History

Coronaviruses were first described in the 1960s from the nasal cavities of patients with the common cold. These viruses were subsequently named human coronavirus 229E and human coronavirus OC43.

Diseases caused by coronaviruses

Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Six different currently known strains of coronaviruses infect humans. The much publicized human coronavirus, SARS-CoV which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections.

Coronaviruses are believed to cause a significant percentage of all common colds in human adults. Coronaviruses cause colds in humans primarily in the winter and early spring seasons. The significance and economic impact of coronaviruses as causative agents of the common cold are hard to assess because, unlike rhinoviruses (another common cold virus), human coronaviruses are difficult to grow in the laboratory. Coronaviruses can cause pneumonia, either direct viral pneumonia or a secondary bacterial pneumonia, and bronchitis, either direct viral bronchitis or a secondary bacterial bronchitis.

In chickens, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the uro-genital tract. The virus can spread to different organs throughout the chicken.

Coronaviruses also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and Bovine coronavirus, which both result in diarrhea in young animals. Feline coronavirus: two forms, Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. Similarly, there are two types of coronavirus that infect ferrets: Ferret enteric coronavirus causes a gastrointestinal syndrome known as epizootic catarrhal enteritis (ECE), and a more lethal systemic version of the virus (like FIP in cats) known in ferrets as ferret systemic coronavirus (FSC). There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice.

Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.

Replication

replication of Coronavirus begins with entry to the cell which takes place in the cytoplasm in a membrane-protected microenvironment. Upon entry to the cell the virus particle is uncoated and the RNA genome is deposited into the cytoplasm.

The Coronavirus genome has a 5’ methylated cap and a 3’polyadenylated tail. This allows the RNA to attach to ribosomes for translation.

Coronaviruses also have a protein known as a replicase encoded in its genome which allows the RNA viral genome to be transcribed into new RNA copies using the host cell's machinery. The replicase is the first protein to be made; once the gene encoding the replicase is translated, the translation is stopped by a stop codon. This is known as a nested transcript. When the mRNA transcript only encodes one gene, it is monocistronic.

The RNA genome is replicated and a long polyprotein is formed, where all of the proteins are attached. Coronaviruses have a non-structural protein - a protease - which is able to separate the proteins in the chain. This is a form of genetic economy for the virus, allowing it to encode the greatest number of genes in a small number of nucleotides.

Severe acute respiratory syndrome

In 2003, following the outbreak of Severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV).

The epidemic resulted in over 8,000 infections, about 10% of which resulted in death. X-ray crystallography studies performed at the Advanced Light Source of Lawrence Berkeley National Laboratory have begun to give hope of a vaccine against the disease "since [the spike protein] appears to be recognized by the immune system of the host."

Novel human coronaviruses

Following the high-profile publicity of SARS outbreaks, there has been a renewed interest in coronaviruses among virologists. For many years, scientists knew about only two human coronaviruses (HCoV-229E and HCoV-OC43). The discovery of SARS-CoV added a third human coronavirus.

By the end of 2004, three independent research labs reported the discovery of a fourth human coronavirus. It has been named NL63, NL, and the New Haven coronavirus by different research groups. The three labs are still arguing over which one discovered the virus first and has the right to name it.

Early in 2005, a research team at the University of Hong Kong reported finding a fifth human coronavirus in two patients with pneumonia. They named it Human coronavirus HKU1.

In September 2012, a sixth new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially Middle East respiratory syndrome coronavirus (MERS-CoV)

The World Health Organisation accordingly issued a global alert The WHO update on 28 September 2012 said that the virus did not seem to pass easily from person to person. However, on May 12, 2013, a case of contamination from human to human in France was confirmed by the French Ministry of Social Affairs and Health. In addition, cases of person-to-person transmission have been reported by the Ministry of Health in Tunisia. Two confirmed cases seem to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia.

By Oct. 30 2013, there were 124 cases and 52 deaths in Saudi Arabia. After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Corona Virus-Erasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV).

In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited 4 different hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside of the Middle East.

Listing of human coronaviruses

Coronaviruses in veterinary medicine

Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the early 1970s. Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.

Listing of coronaviruses in domestic animals

(listed following their estimated economical importance)

Another new veterinary disease, Porcine epidemic diarrhea virus, has emerged around the world. Its economic importance is as yet unclear, but shows high mortality in piglets.

Taxonomy

Evolution

The most recent common ancestor of the coronavirus has been placed at 8,000 years BC. They may be considerably older than this.

Another estimate places the most recent common ancestor (MRCA) of all coronaviruses ~8100 BC. The MRCA of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus have been placed at ~2400 BC, ~3300 BC, ~2800 BC and ~3000 BC, respectively. It appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source with bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.

Bovine coronavirus and canine respiratory coronavirus diverged from a common ancestor in 1951. Bovine coronavirus and human coronavirus OC43 diverged in 1899. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century.

Another estimate suggests that human coronavirus OC43 diverged from bovine coronavirus in 1890.

The MRCA of human coronavirus OC43 has been dated to the 1950s.

Middle East respiratory syndrome coronavirus although related to several bat species appears to have diverged from these several centuries ago.

The most closely related bat coronovirus and the SARS coronavirus diverged in 1986.

A path of evolution of the SARS virus and keen relationship with bats have been proposed. The authors suggest that the coronaviruses have been coevolved with bats for a long time and the ancestors of SARS virus first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets and finally to humans.

Alpaca coronavirus and human coronavirus 229E diverged before 1960.

The human coronavirus NL63 and a bat coronovirus shared an MRCA 563 to 822 years ago.