Virus World

IMPORTANCE

Parts of Southeast Asia where human and bat population densities are highest could be infection hotspots, a study finds. Tens of thousands of people in Southeast Asia could be infected with coronaviruses related to SARS-CoV-2 each year, a study published yesterday (August 9) in Nature Communications estimates. The research, which first appeared as a preprint last September, analyzed the geographic ranges of 26 bat species and found their habitat overlapped regions where half a billion people live, representing an area larger than 5 million square kilometers, reports Reuters. Analyzing that data along with estimates of the number of people who exhibited detectable coronavirus antibodies predicted that approximately 66,000 potential infections occur each year. Stephanie Seifert, a virus ecologist at Washington State University in Pullman who was not involved in the research, tells Nature that the work “highlights how often these viruses have the opportunity to spillover.” The study coauthors considered the geographic ranges of bats known to host SARS-related viruses—primarily horseshoe bats (family Rhinolophidae) and Old World leaf-nosed bats (family Hipposideridae). They found hot spots of potential spillover events in southern China, parts of Myanmar, and the Indonesian island of Java—where both bat and human populations are particularly dense, reports Nature.

Most of these SARS-related viruses don’t easily spread among humans or cause illness. But study coauthor Peter Daszak tells Nature that with enough infections “raining down on people, you will eventually get a pandemic.” However, Alice Hughes, a conservation biologist at the University of Hong Kong who was not involved in the work, tells Nature that this analysis relies on outdated and low-resolution geographical range data. “What they are trying to do is very valuable and needs to be done, but it has to be done with more finesse,” she says. The study authors argue their research can focus spillover monitoring to high-risk regions in order to identify outbreaks sooner. Renata Muylaert, a disease ecologist at Massey University in New Zealand who was not involved in the research, agrees, telling Nature, “The article has considerable significance for surveillance.” This analysis looked only at bat-to-human spillover events and did not consider infections that first transmit from bats to an intermediate animal and later to humans. Daszak tells Nature that there were limited data on that type of event, but that including them would have “massively increased the estimated risk of spillovers.”

Scientists continue to investigate the role of toilets in the spread of coronavirus. The discovery of coronavirus in the bathroom of an unoccupied apartment in Guangzhou, China, suggests the airborne pathogen may have wafted upwards through drain pipes, an echo of a large SARS outbreak in Hong Kong 17 years ago. Traces of SARS-CoV-2 were detected in February on the sink, faucet and shower handle of a long-vacant apartment, researchers at the Chinese Center for Disease Control and Prevention said in a study published this month in Environment International. The contaminated bathroom was directly above the home of five people confirmed a week earlier to have COVID-19.  The scientists conducted “an on-site tracer simulation experiment” to see whether the virus could be spread through waste pipes via tiny airborne particles that can be created by the force of a toilet flush. They found such particles, called aerosols, in bathrooms 10 and 12 levels above the COVID-19 cases. Two cases were confirmed on each of those floors in early February, raising concern that SARS-CoV-2-laden particles from stool had drifted into their homes via plumbing.

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking.

Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19. Vaccines and targeted therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently lacking.

Here, the authors report a human monoclonal antibody capable of neutralizing both authentic SARS-CoV and SARS-CoV-2 by targeting a common epitope.

Published in Nature Comm. (May 4, 2020):

https://doi.org/10.1038/s41467-020-16256-y

How contagious is the virus?

The scale of an outbreak depends on how quickly and easily a virus is transmitted from person to person. While research has just begun, scientists have estimated that each person with the Wuhan coronavirus could infect somewhere between 1.5 and 3.5 people without effective containment measures. That would make the new virus roughly as contagious as SARS, another coronavirus that circulated in China in 2003 and was contained after it sickened 8,098 people and killed 774. Respiratory viruses like these can travel through the air, enveloped in tiny droplets that are produced when a sick person breathes, talks, coughs or sneezes. These droplets fall to the ground within a few feet. That makes the virus harder to get than pathogens like measles, chickenpox and tuberculosis, which can travel a hundred feet through the air. But it is easier to catch than H.I.V. or hepatitis, which spread only through direct contact with the bodily fluids of an infected person.

How contagious is the virus?

The scale of an outbreak depends on how quickly and easily a virus is transmitted from person to person. While research has just begun, scientists have estimated that each person with the Wuhan coronavirus could infect somewhere between 1.5 and 3.5 people without effective containment measures. That would make the new virus roughly as contagious as SARS, another coronavirus that circulated in China in 2003 and was contained after it sickened 8,098 people and killed 774. Respiratory viruses like these can travel through the air, enveloped in tiny droplets that are produced when a sick person breathes, talks, coughs or sneezes. These droplets fall to the ground within a few feet. That makes the virus harder to get than pathogens like measles, chickenpox and tuberculosis, which can travel a hundred feet through the air. But it is easier to catch than H.I.V. or hepatitis, which spread only through direct contact with the bodily fluids of an infected person.....

Additional information from study published in New England J. Medicine (Jan. 29, 2020):

https://doi.org/10.1056/NEJMoa2001316

The first confirmed U.S. case of a traveler infected with the virus behind China’s continuing pneumonia outbreak has health authorities on alert to prevent it from spreading. The patient—a man in his 30s—returned from the country’s city of Wuhan (where the virus appears to have originated) to his home in Snohomish County in Washington State on January 15. He developed symptoms and sought treatment from his doctor on January 19, and a day later, a real time reverse transcription-polymerase chain reaction (rRT-PCR) test confirmed he had the virus. The patient appears to be doing well and was being treated this week at a hospital in Everett, Wash., and placed in isolation out of an abundance of caution, said a spokesperson for the U.S. Centers for Disease Control and Prevention in a news briefing on Tuesday afternoon.

The virus, called 2019 novel coronavirus (2019-nCoV), is known to have infected hundreds of people so far, and Chinese authorities have now reported at least 17 deaths. It was first identified in Wuhan late last year and is believed to have jumped from animals to humans at a local seafood market that also sold other wild animal meat. Authorities have since confirmed cases of human-to-human transmission. The pathogen is a coronavirus, a member of a family of viruses that include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which caused major outbreaks in 2003 and 2012, respectively. Cases of 2019-nCoV have been confirmed in several other countries, including Thailand, Japan and South Korea. Three U.S. airports—in San Francisco, Los Angeles and New York City—began screening travelers from Wuhan last week. Such measures have now been expanded to two more airports—in Atlanta and Chicago—and passengers traveling to the U.S. from Wuhan will be funneled to those five locations. The risk to the U.S. public is low at this time, according to the Centers for Disease Control and Prevention. But the agency says it is working closely with other health organizations to contain the virus’s spread. 

National Institute of Allergy and Infectious Diseases director Anthony Fauci has been been closely following developments related to the new virus. Scientific American spoke with Fauci about 2019-nCoV’s likely mode of transmission, its similarity to other coronaviruses and the question of whether a vaccine is on the horizon....

More than 100 staffers from the US Centers for Disease Control and Prevention are being deployed to three US airports to check passengers arriving from Wuhan, China, for fever and other symptoms of a mysterious new virus that's killed two and infected dozens in China, the CDC announced Friday. It's a highly unusual step. The last time the CDC did routine passenger health screening was during the 2014 Ebola outbreak, according to Dr. Martin Cetron, director of the CDC's division of global migration and quarantine. "I've been here since 1996, and that's the only other time we've ever done this -- for Ebola," Cetron said.

The USAID’s Predict program, which conducted animal virus surveillance and disease outbreak prevention training, is ending after its 10-year funding run according to The New York Times. Launched after an H5N1 bird flu outbreak, Predict was part of an effort to search for previously undiscovered zoonotic diseases, which are passed from animals to humans. Viruses such as AIDS, SARS, MERS, Ebola, and certain influenza strains originally came from animals.

Researchers found more than 1,000 new viruses from animal samples collected during the program’s run, including a new Ebola strain. In addition, it provided disease outbreak prevention training for thousands of people and strengthened medical laboratories in developing countries. The program, which partnered with universities, conservation groups, and nonprofits to track, monitor, and prevent disease, was shut down at the end of its 10-year funding cycle [did the article explain why it wasn’t continued?]. Some public health officials worry that its end could leave the world more vulnerable to dangerous epidemics. “Predict needed to go on for 20 years, not 10,” says Jonathan Epstein, a veterinarian with the nonprofit EcoHealth Alliance, a Predict partner organization, to the Times.

Some projects will be continued by other government agencies, but the focus on training health workers abroad will be reduced. The end of Predict “is really unfortunate, and the opposite of what we’d like to see happening,” Gro Harlem Brundtland, the former prime minister of Norway and the former World Health Organization director-general, tells the Times. “Americans need to understand how much their health security depends on that of other countries, often countries that have no capacity to do this themselves,” she adds.

The Antiviral Program for Pandemics (APP) team, along with experts from across the National Institutes of Health (NIH) and Biomedical Advanced Research and Development Authority (BARDA), has drafted Target Product Profiles (TPPs) for potential direct-acting antiviral therapeutics candidates targeting several key viruses of pandemic potential.  These TPPs should be considered ‘living documents’ that are never final but may be useful starting points for consideration by therapeutics developers who are drafting TPPs for their specific candidates.  Also, the example TPPs are not intended to provide details about product requirements for funding or other support from USG or other funders.  Instead, these sample TPPs are being provided as tools for scientists working toward therapeutics product development of direct-acting antivirals for use in potential future outbreaks or pandemics. We are happy to receive feedback on these sample TPPs and may make updates/revisions or add TPPs for additional clinical indications in the future, so please monitor this page for updates and send any feedback to APPSubmissions@mail.nih.gov

Pandemic hunting scientists warn of a 'perfect storm' for new diseases to emerge from wildlife. In the last 20 years, we've had six significant threats - SARS, MERS, Ebola, avian influenza and swine flu," Prof Matthew Baylis from the University of Liverpool told BBC News. "We dodged five bullets but the sixth got us. "And this is not the last pandemic we are going to face, so we need to be looking more closely at wildlife disease." As part of this close examination, he and his colleagues have designed a predictive pattern-recognition system that can probe a vast database of every known wildlife disease.

Across the thousands of bacteria, parasites and viruses known to science, this system identifies clues buried in the number and type of species they infect. It uses those clues to highlight which ones pose most of a threat to humans. If a pathogen is flagged as a priority, scientists say they could direct research efforts into finding preventions or treatments before any outbreak happens. "It will be another step altogether to find out which diseases could cause a pandemic, but we're making progress with this first step," Prof Baylis said.

Many scientists agree that our behaviour - particularly deforestation and our encroachment on diverse wildlife habitats - is helping diseases to spread from animals into humans more frequently. According to Prof Kate Jones from University College London, evidence "broadly suggests that human-transformed ecosystems with lower biodiversity, such as agricultural or plantation landscapes, are often associated with increased human risk of many infections". "That's not necessarily the case for all diseases," she added. "But the kinds of wildlife species that are most tolerant of human disturbance, such as certain rodent species, often appear to be more effective at hosting and transmitting pathogens....

The coronavirus that causes COVID-19, SARS-CoV-2, can survive for several hours in an aerosolized form and for up to three days on plastic and steel surfaces, researchers reported Tuesday (March 10) on medRxiv. While the detection of viable virus means it’s theoretically possible to transmit the disease from contaminated surfaces or from the air—in addition to the typical route of having larger droplets land directly on a new host after an infected person, say, coughs in their proximity—“We’re not by any way saying there is aerosolized transmission of the virus,” coauthor Neeltje van Doremalen of the National Institute of Allergy and Infectious Diseases tells the Associated Press.

The authors applied SARS-CoV-2 and SARS-CoV, the virus that caused the SARS outbreak of 2003, to plastic, stainless steel, copper, and cardboard in the lab and created aerosolized viruses using a nebulizer. They found viable SARS-CoV-2 three hours after the virus was aerosolized and suspended in the air within a drum, and on surfaces four hours, 24 hours, and 2–3 days after it was deposited to copper, cardboard, and steel or plastic, respectively. SARS-CoV lasted about as long, although it lost viability sooner on cardboard and more slowly on copper. The median half-life for SARS-CoV-2 was 13 hours on steel and 16 hours on plastic. “It’s a solid piece of work that answers questions people have been asking,” Julie Fischer, a microbiologist at Georgetown University who was not involved in the study, tells the AP. “What we need to be doing is washing our hands, being aware that people who are infected may be contaminating surfaces,” and not touching our faces....

Published in medRxiv (March 13, 2020):

https://doi.org/10.1101/2020.03.09.20033217 

The second notable feature of SARS-CoV-2 is a predicted polybasic cleavage site (RRAR) in the spike protein at the junction of S1 and S2, the two subunits of the spike protein (Figure 1b)8,9. In addition to two basic arginines and an alanine at the cleavage site, a leading proline is also inserted; thus, the fully inserted sequence is PRRA (Figure 1b). The strong turn created by the proline insertion is predicted to result in the addition of O-linked glycans to S673, T678, and S686 that flank the polybasic cleavage site. A polybasic cleavage site has not previously been observed in related lineage B betacoronaviruses and is a unique feature of SARS-CoV-2. Some human betacoronaviruses, including HCoV-HKU1 (lineage A), have polybasic cleavage sites, as well as predicted O-linked glycans near the S1/S2 cleavage site.

While the functional consequence of the polybasic cleavage site in SARS-CoV-2 is unknown, experiments with SARS-CoV have shown that engineering such a site at the S1/S2 junction enhances cell–cell fusion but does not affect virus entry10. Polybasic cleavage sites allow effective cleavage by furin and other proteases, and can be acquired at the junction of the two subunits of the haemagglutinin (HA) protein of avian influenza viruses in conditions that select for rapid virus replication and transmission (e.g. highly dense chicken populations). HA serves a similar function in cell-cell fusion and viral entry as the coronavirus S protein. Acquisition of a polybasic cleavage site in HA, by either insertion or recombination, converts low pathogenicity avian influenza viruses into highly pathogenic forms11-13. The acquisition of polybasic cleavage sites by the influenza virus HA has also been observed after repeated forced passage in cell culture or through animals14,15. Similarly, an avirulent isolate of Newcastle Disease virus became highly pathogenic during serial passage in chickens by incremental acquisition of a polybasic cleavage site at the junction of its fusion protein subunits....

...It is improbable that SARS-CoV-2 emerged through laboratory manipulation of an existing SARS-related coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for human ACE2 receptor binding with an efficient binding solution different to that which would have been predicted. Further, if genetic manipulation had been performed, one would expect that one of the several reverse genetic systems available for betacoronaviruses would have been used. However, this is not the case as the genetic data shows that SARS-CoV-2 is not derived from any previously used virus backbone17. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in a non-human animal host prior to zoonotic transfer, and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage in culture could have given rise to the same observed features...

Mandarin version of the article available at: 

http://virological.org/uploads/short-url/dHpDmgjWKLNlBztUWteEJZq4Pvw.pdf

(NOTE: the findings below, originally published in the J. Medical Virology, have been widely DISPUTED by others in the field) 

Snakes -- the Chinese krait and the Chinese cobra -- may be the original source of the newly discovered coronavirus that has triggered an outbreak of a deadly infectious respiratory illness in China this winter. The many-banded krait (Bungarus multicinctus), also known as the Taiwanese krait or the Chinese krait, is a highly venomous species of elapid snake found in much of central and southern China and Southeast Asia. The illness was first reported in late December 2019 in Wuhan, a major city in central China, and has been rapidly spreading. Since then, sick travelers from Wuhan have infected people in China and other countries, including the United States.

Using samples of the virus isolated from patients, scientists in China have determined the genetic code of the virus and used microscopes to photograph it. The pathogen responsible for this pandemic is a new coronavirus. It's in the same family of viruses as the well-known severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which have killed hundreds of people in the past 17 years. The World Health Organization (WHO) has named the new coronavirus 2019-nCoV....

Published in the Journal of Medical Virology (22 January 2020):

https://doi.org/10.1002/jmv.25682

Chinese health authorities have confirmed that the deadly new virus sweeping through the country can be spread from person to person, the World Health Organization said it would consider declaring an international public health emergency. Zhong Nanshan, a respiratory expert and the man who helped control the deadly severe acute respiratory syndrome (Sars) outbreak in 2002 to 2003, told state media that two people in Guangdong province in southern China caught the disease, a novel coronavirus, from family members. Health authorities in the central city of Wuhan, where a seafood market has been identified as the centre of the outbreak, said on Tuesday that an 89-year-old man became the fourth person to die from the virus. China’s National Health Commission also reported that 14 health workers have been infected but did not give any more details.

Chinese researchers say they have identified a new virus behind an illness that has infected dozens of people across Asia, setting off fears in a region that was struck by a deadly epidemic 17 years ago. There is no evidence that the new virus is readily spread by humans, which would make it particularly dangerous, and it has not been tied to any deaths. But health officials in China and elsewhere are watching it carefully to ensure that the outbreak does not develop into something more severe.

Researchers in China have “initially identified” the new virus, a coronavirus, as the pathogen behind a mysterious, pneumonialike illness that has sickened 59 people in the city of Wuhan and caused a panic in the central Chinese region, the state broadcaster, China Central Television, said on Thursday. They detected this virus in 15 of the people who fell ill, the report said. The new coronavirus “is different from previous human coronaviruses that were previously discovered, and more scientific research is needed for further understanding,” the report said. Coronaviruses are a large family of viruses that infect animals and people. Some cause only the symptoms known as the common cold, although many other viruses also do that.

The announcement signals that researchers are making progress in containing the outbreak, but Asian officials are not likely to relax their vigilance until they learn more. The disease has evoked memories of the outbreak of SARS, or severe acute respiratory syndrome, in 2003. SARS, a respiratory disease and also a coronavirus, spread from southern China in 2003 and infected more than 3,000 people, killing 774. China initially covered up the extent of the SARS outbreak and was criticized by health officials around the world for doing so. On Thursday, the World Health Organization praised the Chinese response to the new outbreak and said it did not recommend any restrictions on trade or travel to China because of the virus....