Writer : Yan Jiaxin / http://blog.sciencenet.cn/blog-347754-1254954.html / Direct translation / Image courtesy : Lukas Schulze / Getty Images
PNAS paper warning:
A coronavirus that has spread from bats to pigs may pose another threat to human health.
After the SARS-CoV (SARS-CoV) pandemic in 2003, the results of sampling and testing in wild animals told us that bats harbor many viruses similar to SARS-CoV, some of which have the potential to cause pandemics. . But after the epidemic, only a handful of laboratories in the world continue to study SARS-CoV, and large pharmaceutical companies have lost interest in this virus, because this virus seems to have disappeared from the surface of the earth and is related to SARS coronavirus The research on antiviral drugs or vaccines in China has subsequently become a money-losing business, and it seems that there is no hope of making money in the future, so almost all related research has been abandoned halfway.
Therefore, when the novel coronavirus suddenly appeared at the end of 2019, humans were completely unable to prevent the rapid spread of the virus on a global scale. If we had the foresight and provided financial support in advance to develop related antiviral drugs or vaccine research and development, the pandemic caused by the coronavirus might have avoided the outbreak, and it would have been terminated in time after the outbreak.
At present, the struggle between humans and the novel coronavirus is still in full swing, and the threat of a new and potentially equally dangerous coronavirus is emerging on the horizon. According to research data provided by a research paper (see Reference 1) published in PNAS (Proceedings of the National Academy of Sciences) on August 18 this year, a coronavirus that spreads from bats to pigs may pose a risk and another threat to human health.
In the past 80 years, a variety of coronaviruses have caused widespread outbreaks of related diseases and huge economic losses in pigs. These coronaviruses that infect pigs include transmissible gastroenteritis virus (TGEV) , Porcine respiratory coronavirus (PRCV), porcine epidemic diarrhea coronavirus (PEDV), porcine hemagglutinating encephalomyelitis virus (PHEV) and porcine delta coronavirus (porcine deltacoronavirus, PDCoV).
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that may have evolved from the closely related bat coronavirus HKU2, which is found in China and other regions Rhinolophus spp. (Horseshoebats, Rhinolophus spp.). The chrysanthemum bat near the outbreak point of the local epidemic has a virus HKU2 with a highly similar sequence to the SADS-CoV strain, indicating that SADS-CoV may have originated from bats (2). From October 2016 to 2019, there have been multiple outbreaks of the novel coronavirus in pig herds across China, causing outbreaks of deadly piglet diseases. SADS-CoV infection is related to acute diarrhea and vomiting, and the mortality rate of piglets under 5 days is 90% (2, 3, 4). China’s swine industry is widely distributed and there are many opportunities for humans to contact pigs. Therefore, it is necessary to increase investment to understand the virus and its pathogenic potential in mammals, especially whether SADS-CoV may infect humans.
The concept of One Health recognizes that the health of humans, animals and the environment are closely linked. In the 21st century, there are three new human coronaviruses and three new porcine coronaviruses suddenly appearing and spreading around the world, indicating the urgent need to adopt appropriate strategies to identify high-risk zoonotic coronaviruses in time. There are four early contemporary human coronaviruses: HCoV NL63, HCoV 229E, HCoV OC43 and HCoV HKU1, which can cause common colds in children and adults. These viruses may have originated from bats, rodents or cattle strains before the early 20th century. In this century, three new highly pathogenic human coronaviruses have emerged, including the severe acute respiratory syndrome coronavirus (SARS-CoV) that first appeared in China in 2003 and the Middle East respiratory syndrome coronavirus that appeared in the Middle East in 2012 (MERS-CoV). SARS-CoV and MERS-CoV lead to the rapid development of atypical pneumonia into acute respiratory distress syndrome, with mortality rates of 10% and 35%, respectively. The atypical SARS and SARS-like coronaviruses with potential to spread among the population have been spreading among bat populations in Southeast Asia and other regions, and in 2019 evolved into SARS-CoV-2 that caused unprecedented harm in the world. Obviously, the cross-species transmission potential of the coronavirus that causes zoonotic diseases to humans and other important domesticated species is still high, and it is a pathogen that should be paid attention to globally (2).
According to the classification of viruses, the coronavirus family is divided into four genera: α, β, γ, and δ. SADS-CoV belongs to the genus Alphacoronavirus (Alphacoronavirus, α-CoV), and is closely related to the coronaviruses HCoV-229E and HCoV-NL63 (also classified as the genus Alphacoronavirus) that can cause the common cold in humans. However, the human anti-HCoV-NL63 serum cannot prevent SADS-CoV infection (it cannot neutralize rSADS-CoV), indicating that the viruses belonging to the human alphacoronavirus have a limited cross-protection effect in herd immunity.
It is known that many coronavirus infections require different cell receptors. For example, SARS-CoV and SARS-CoV2 require angiotensin converting enzyme 2 (ACE2), MERS-CoV requires DPP, and HCoV-229E requires APN. Antibodies against these cellular proteins did not prevent the cells from being infected with SADS-CoV, indicating that there must be different cell receptors that trigger the infection of the virus.
Since the coronavirus has caused serious economic losses in the pork industry, and pigs are often the key intermediate host for human disease outbreaks, the authors of the above PNAS paper synthesized a full-length infectious clone of the SADS-CoV genome and constructed a wild type ( r) SADS-CoV and the derivative recombinant virus rSADS-CoVtRFP that can express tomato red fluorescent protein (tRFP), and use these viruses to study virus replication, transcription programs and gene expression in vitro. The author observed the proliferation of pig, primate, cat and human cell lines after being infected with the virus, and evaluated the sensitivity and permissivity of various cells to SADS-CoV. The ultimate goal is to evaluate humans. Susceptibility to cross-species transmission and replication of SADS-CoV.
"The results show that: rSADS-CoV can effectively replicate in a variety of animal and primate continuous cell lines, including human liver cancer and rectal cancer cell lines. Of particular concern is that rSADS-CoV can effectively replicate in several different primary human lung cells and primary human intestinal cells. This indicates that SADS-CoV has the inherent potential for cross-species transmission and is a potential high-risk new coronavirus pathogen.
What should we do to prevent another potentially devastating pandemic caused by a coronavirus similar to SARS-CoV-2?
There is no doubt that antiviral drugs that can inhibit SADS-CoV (and a large number of bat SARS-like coronaviruses) and safe and effective broad-spectrum vaccines that can prevent all coronavirus infections should be actively explored. In addition, people who are in regular contact with pigs should regularly check for the presence of SADS-CoV-like viruses.
After the SARS-CoV-2 pandemic, we can no longer ignore the threat posed to humans by the coronavirus and other viruses that spread in bats, rodents and other animals. Using the relevant scientific knowledge gained before 2019, we could have prevented the SARS-CoV-2 pandemic. We should learn from the painful lesson and be fully prepared to kill the next pandemic of the coronavirus in the bud.
References:
1. C.-E. Edwards et al., Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection (the replication of porcine acute diarrhea syndrome coronavirus in human primary cells reveals the potential for infection Susceptibility), PNAS, first published October 12, 2020; https://doi.org/10.1073/pnas.2001046117
2. P. Zhou et al., Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556, 255–258 (2018).
3. L. Gong et al., A new bat-HKU2-like coronavirus in swine, China, 2017. Emerg. Infect. Dis. 23, 1607–1609 (2017).
4. L. Zhou, The re-emerging of SADS-CoV infection in pig herds in southern China. Transbound. Emerg. Dis. 66, 2180–2183 (2019).
5. Y.-W. Huang et al., Origin, evolution, and genotyping of emergent porcine epidemicdiarrhea virus strains in the United States. mBio 4, e00737-13 (2013)
6. C.-M. Lin, L. J. Saif, D. Marthaler, Q. Wang, Evolution, antigenicity and pathogenicity of global porcine epidemic diarrhea virus strains. Virus Res. 226, 20–39 (2016)
See also:
Yixuan J. Hou etal., Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection, Peter Daszak ed., PNAS, https://www.pnas.org/content/early/2020/10/06/2001046117; https://doi.org/10.1073/pnas.2001046117
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