Here is a scientific primer to help you understand this pathogen better  

In less than a month, a mysterious outbreak of pneumonia that surfaced in the Huanan Seafood Market in China’s Hubei province circled the globe, creating worldwide panic. The illnesses were linked to the Wuhan coronavirus (tentatively named the 2019 Novel Coronavirus, 2019-nCoV), named for the city that is at the epicenter of the outbreak. More than 2,900 confirmed cases of the infection have been reported as of this writing. Most are in China, but it has already spread to other parts of Asia, Europe, and the US. More than 80 have died. These numbers will surely rise until the outbreak is contained. Johns Hopkins University is tracking the number of confirmed cases and deaths.

The pressure is rising on China as it tries to come to grips with a disease that has already outstripped the number of MERS cases, and many fear will rival SARS, which claimed almost 800 lives 17 years ago. In an attempt to contain the spread of the virus, the Chinese government restricted travel for 40 million people on the eve of the Lunar New Year, ordered travel agencies to suspend sales of domestic and international package tours, and parts of the Great Wall and Disneyland in Shanghai closed. The US State Department has chartered flights to evacuate diplomats from Wuhan out of concern for their safety.

Novel viruses all tell their own unique story, but they also share common ground with sister viruses. Here are some questions that will help you better understand coronaviruses.

1) Roughly how many coronaviruses have we identified so far?

There are about 40 coronaviruses officially recognized, named and classified, though there are certainly more than this out in the world. These are divided into four subgroups, alpha, beta, gamma, and delta, based on their genetic and antigenic properties. The majority of these viruses are enzootic, meaning they only infect animals.

There are seven human coronaviruses, most of which were only identified in the past 20 years. These viruses all made the species jump from an animal reservoir, gaining the ability to infect and be transmitted between humans (zoonotic viruses). The most well-known are severe acute respiratory syndrome coronavirus (SARS-CoV), which was identified in 2003 and disappeared in 2004, and Middle East respiratory syndrome coronavirus (MERS-CoV), which was first reported in 2012 and is still endemic in the Arabian Peninsula. They have mortality rates of 15% and 35%, respectively. There were approximately 8096 confirmed SARS cases and 774 deaths. As of 2019, there have been approximately 2494 confirmed MERS cases, over 80% occurring in Saudi Arabia, with 791 deaths.

2) Are there unique characteristics of this virus?

Coronaviruses are enveloped, single-stranded, positive sense RNA viruses. Their genome typically ranges from 26-32 kilobases with a conserved structure, meaning they have the largest genome  out of the RNA viruses. In addition to the replicase genes, encoding the RNA dependent RNA polymerase, the genome encodes four multi-functional structural proteins: Spike (S), nucleocapsid (N), membrane (M), and envelope (E). The S protein mediates binding and fusion of the virus to the host cells, to allow for infection. It forms the characteristic “crown-like” projections on the surface of the virion, giving this family its name. This protein, therefore, is the primary determinant of host range. N binds the genome and helps to mediate assembly of the viral capsid. M functions as the central organizer of virus assembly. Finally, E helps to shape the structure and function of the viral envelope, though its function is not fully understood.

3) It seems that in recent decades some deadly viruses have emerged that are corona-like viruses – SARS, of course, but also MERS, and now this new one out of China. Any theories as to why we are seeing so many of them?

SARS-CoV and MERS-CoV both originated in bats. SARS-CoV is thought to have then been transmitted via infected palm civet cats and racoon dogs to humans at local Chinese markets. Likewise, MERS-CoV spread from bats, via dromedary camels, to humans. Both viruses were then readily transmitted between humans. In both outbreaks, a few people acted as “super-spreaders”, and, with the help of increasingly easy international travel, spread the virus worldwide.

The origins of 2019-nCoV have not yet been identified. Recently a hypothesis based on sequencing data proposed that it spread from bats to snakes being sold at the Huanan Market. While it is currently accepted that the virus originated in bats, the data arguing for the role of snakes as the transmission species has already been criticized. There is also now evidence of easy human to human transmission, which can occur before the onset of symptoms. However, it is still early days and the true scope and lethality of this pandemic remain to be determined.

Biological and societal factors are driving the recent emergence of these viruses. Biologically, the genomes of RNA viruses, including coronaviruses, are relatively unstable and are prone to mutation. Small changes in the spike protein affect the species that the virus can infect. For example, only a 6 amino acid change was needed to allow for SARS-CoV to jump from civet cats to humans. Socially, our new habits in the past ~50 years have contributed these pandemics. Urbanization, especially into formally rural China, has led to an encroachment of humans into the natural reservoirs of these viruses. The continued practice of selling live animals in traditional food markets, where conditions are often less than sanitary, brings humans into close contact with potentially infected animals. Finally, globalization and the corresponding increase in international travel have allowed for the rapid worldwide spread of new viruses. Increased globalization has driven every major viral epidemic in the past century, including the 1918 pandemic influenza, SARS and MERS, Zika, Ebola, and now 2019-nCoV.

4.) How difficult is it to make a vaccine against a coronavirus? Are there particular challenges about their structure that make it difficult for vaccines to induce antibodies?

Following the outbreak of SARS-CoV in 2003, many groups began to work towards the development of a vaccine. However, the virus disappeared in mid-2004 and has not re-emerged. This, combined with the emergence of MERS-CoV in 2012, shifted most of the efforts towards developing a MERS-CoV-specific vaccine. The first MERS-CoV vaccine candidate was developed in 2013 began clinical trials in 2015.

There are currently four MERS-CoV vaccine candidates in early clinical trials, all using the S protein as the antigen because it has been shown to be highly immunogenic, capable of eliciting both cellular and humoral immunity. While cellular responses are critical in fighting an active infection, it has been shown in animal models that it is the antibody responses that confer long-lasting protection against MERS. There is nothing specific about the structure of coronaviruses that would prevent the development of a vaccine. It is theoretically no more difficult to develop a vaccine for coronaviruses than it is for most other viruses. However, developing a vaccine is not an easy task! Moreover, developing a vaccine that confers protective immunity at a mucosal site, such as the lung, brings along its own set of difficulties. There are also practical considerations around bringing a vaccine to market. It typically can take 10 years or more to bring a vaccine through clinical trials (plus additional time for candidate development), costing hundreds of millions of dollars. Many of the candidates have only just begun Phase 1 clinical trials. It is therefore likely that it will be at least 5-8 more years until one reaches market, assuming at least one of these vaccines is able to pass through the clinical trials.

5.) Lastly, how virulent are coronaviruses compared to other viruses.

Virulence refers to a pathogen’s ability to infect or damage a host. We can break it down into three questions: (1) how many cases of illness does the virus cause, (2) how deadly is the virus, and (3) how easily does the virus spread from one person to the next? The table below summarizes the three recent coronaviruses to other well-known viruses. Transmissibility in epidemiology is defined by the basic reproduction number, R0, which can be thought of the number of cases that one cases generates. Generally, the bigger the R0 is, the harder it is to control.

Virus

Number of Cases

Approximate Lethality Rate

R0 (transmissibility)

SARS-CoV (2003-2004)

8,096

15%

2-5

MERS-CoV (Since 2012)

2,494

35%

Not determined

2019-nCoV (As of Jan 27, 2020)

2,886

3%

Not determined

Ebola (2014-15 West Africa outbreak)

~29,000

33%

1-2

1918 Influenza (worldwide)

500 million

2.5%

2-3

Seasonal Influenza (USA only)

20-50 million/year

<0.1%

1.3

Smallpox (prior to eradication, worldwide)

15 million/year

30%

5-7

Measles (prior to vaccination, USA only)

3-4 million/year

<0.01%

12-18

Polio (prior to vaccination, USA only)

10-60 thousand/year

5-20%

5-7

Compared to other well-known viruses and pandemics, the numbers for 2019-nCoV are very low. However, new data is emerging daily about the outbreak, its ability to spread, and its lethality. We therefore do not have a clear understanding of how this virus will compare to others. The numbers of the other viruses reveal the potential devastation that a pandemic virus can cause. For example, the 1918 influenza is estimated to have infected 1/3 of the world and killed 50 million. Prior to its eradication, smallpox infected 15 million and killed 5 million every year. This is why governments are taking aggressive and proactive measures to limit the outbreak and why there is such an intense focus on this virus in the media, despite the relatively low numbers reported thus far.

Information from the CDC, WHO, and journal articles were used to help compiled this Q&A. Do you have more questions. Reach out to Eureka and we will try to answer them.