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Table of Contents
EDITORIAL
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 284-286

Is COVID-19 man-made?


Department of Head and Neck Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission30-Apr-2020
Date of Decision04-May-2020
Date of Acceptance06-May-2020
Date of Web Publication19-Jun-2020

Correspondence Address:
Pankaj Chaturvedi
Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_166_20

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How to cite this article:
Chaturvedi P, Ramalingam N, Singh A. Is COVID-19 man-made?. Cancer Res Stat Treat 2020;3:284-6

How to cite this URL:
Chaturvedi P, Ramalingam N, Singh A. Is COVID-19 man-made?. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Sep 18];3:284-6. Available from: http://www.crstonline.com/text.asp?2020/3/2/284/287216



In 2015, the Wuhan Institute of Virology (WIV) was upgraded to the National Biosafety Laboratory (Level 4), the first of its kind in China, at a cost of 300 million Yuan ($44 million).[1] The lab was involved in the research of coronaviruses (CoVs) and the causative agents of the severe acute respiratory syndrome (SARS) outbreak in 2003. In 2015, Li et al. published reports about the species of bats acting as natural reservoirs for SARS-like CoVs (SL-CoVs),[2] and pointed out the genetic diversity of the viruses in bats, highlighting the possibility of them infecting the humans. The transmission from palm civets to humans occurred when the civets came into human contact in the live animal markets.[3] As the pools of CoVs in bats were limited, the likelihood of a future emergence of this viral outbreak was never anticipated.[4]

However, when it was proven that a chimeric virus containing the SHC014 spike in a SARS-CoV backbone causes robust infections in both human airway cultures and mice,[5] a warning was issued that the starting materials required for SARS-like emergent strains were already circulating in animal reservoirs. A research team in China that spent 5 years in the Shitou caves of Yunnan sampling from the bats issued a similar warning and raised alerts for a potential disease outbreak if adequate precautions were not taken. By December 2019, the first cluster of cases of infection with a novel CoV was reported in China.

Naturally, the origins of the epidemic were investigated. The WIV published reports stating that the new strain of CoV had bats as the “probable” source.[6],[7] All the studies of Shi Zheng Li, the lead virologist from the institute, on bat-related CoVs were centered in the southern, subtropical areas of Yunnan. However, the outbreak occurred in Wuhan, which is almost 900 km from Yunnan. Samples from the infected patients were compared with those from the bats, but none of them matched. If not from bats, where did this novel strain of CoV come from? The Government of China conducted an investigation and reported a wildlife market, 10 miles away from the virology institute, as the epicenter. Though the Chinese government discredited the possibility of a lab origin based on the genetic studies, the distance of the epicenter from the bat caves raises questions.

The theory of lab origin gains credibility from seemingly unrelated, but nevertheless solid and tangible facts. The institute called for research job openings on November 18, 2019, and December 24, 2019.[8] These urgent advertisements tell us about the kind of research taking place in the labs and also underline the fact that the Chinese knew about the possibilities of novel strains even before the outbreaks that warranted research. The lab then generated a chimeric virus from the SARS-CoV using the reverse genetics approach and reported the potential for human emergence.[5] The leak could have happened from this lab.

On February 6, 2020, scientists from the South China University pointed out that the intermediate host, the horseshoe bat, was not available in the wet market and did not live in the Wuhan area.[9] The only place the bats existed in the locality was the research facility, which is just about a 100 yards from the Wuhan wet market. The horseshoe bats are found only in the Yunnan province. However, they are neither consumed as food in the city, nor are they ever traded in the markets. The paper also states that in the Wuhan Center for Disease Control and Prevention located 280 m from the market, the extraction and sequencing of the DNA and RNA from caged animals could have been a potential source of the pathogen. This center is also adjacent to the Union Hospital, where the first groups of doctors were infected during this epidemic. Curiously, the lead author has now retracted the paper saying that it was based on mere speculations and not on solid proof.[8]

Not surprisingly, two papers posted on the websites of the Fudan University and the China University of Geosciences met a similar fate. They were removed following a new policy mandating government approval for publishing academic papers about COVID-19.[10] These clampdowns support the theory of a lab leak. The theory gets bolstered by the classified cables from the US embassy in China in January 2020.[11] It was reported that the labs were conducting high-risk studies with a lack of appropriately trained technicians and investigators. There were concerns of undue risks being taken. Similar concerns were raised about the nearby Wuhan Center for Disease Control and Prevention lab. It appears that the leaks cannot be ruled out entirely.

An Indian paper published in January, which has now been retracted, theorized genetically altered insertions in the genome of the novel CoV similar to the genetic sequences of human immunodeficiency virus (HIV) and Ebola.[12],[13] They found it quite unlikely for a virus to have acquired such unique insertions naturally in a short duration. These artificially engineered changes were thought to increase the range of host cells that the 2019-nCoV can infect. This paper was taken down amidst criticism, but research from the Nankai University in Tianjin reports similar findings.[14] This can be considered an evidence for the virus being man-made.

Lastly, the doctors who were the first responders were allegedly clamped down by the government. Li Wenliang who sounded the alarm on the Wuhan CoV on WeChat [15] was taken to the police station where he was warned against spreading rumors. Unfortunately, he succumbed to the disease subsequently. These doctors were advised by the government, “not to mislead the public” and to “refrain from publishing any unauthorized information.” They were also told to “resist all kinds of rumors and clarify and guide false opinions and discussions.”[16]

For a pragmatic view on the issue, it is imperative on our part to look at arguments against the lab origin of COVID-19. Rhinolophus affinis bat and Malayan pangolins (Manis javanica) contain CoVs similar to the SARS-CoV-2. However, the receptor-binding domains (RBDs) of viruses isolated from these two sources were markedly different from the human SARS-CoV-2 RBDs, which have a lower affinity to the angiotensin-converting enzyme 2 (ACE2) receptors. Theoretically, this may indicate a process of natural selection in the animal host before transfer.[17] Secondly, this adaptation may have occurred after the zoonotic transfer into the humans. A progenitor of SARS-CoV-2 after infecting humans may have acquired genomic features through adaptation during undetected human-to-human transmission.[17] Retrospective serological studies could answer these questions. Lastly, the optimal RBD sequence for the human receptors as predicted using computer models, significantly differs from the RBD sequences with high binding affinity isolated from the humans.[18] If artificial engineering was the source, this particular RBD sequence would not have been preferred as it did not have a high binding affinity as predicted in the computer models. This underscores the possibility of natural selection.

Nevertheless, many evidences seem to give credence to the theory of a man-made virus that has leaked from the lab into the community. Although it seems unethical to point fingers at this time when our efforts are required elsewhere, one cannot be contented with the community origin theory put forward by the Chinese government when the evidences say otherwise. It is imperative on the part of the health-care community to get to the bottom of this in order to prevent future occurrences of man-made pandemics, simply because we may never have a chance otherwise.



 
  References Top

1.
Available from: http://english.whiov.cas.cn/News/Event s/201502/ t20150203_135923.html. [Last accessed 2020 May 24].  Back to cited text no. 1
    
2.
Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 2005;310:676-9.  Back to cited text no. 2
    
3.
Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med 2004;10:S88-97.  Back to cited text no. 3
    
4.
Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol 2013;11:836-48.  Back to cited text no. 4
    
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Menachery VD, Yount BL Jr., Debbink K, Agnihothram S, Gralinski LE, Plante JA, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 2015;21:1508-13.  Back to cited text no. 5
    
6.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.  Back to cited text no. 6
    
7.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv 2020;22:914952.  Back to cited text no. 7
    
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Available from: https://www.ccn.com/hiv-ebola-like-muta tions-suggest-coronavirus-leak ed-from-a-lab/. [Last accessed 2020 May 24].  Back to cited text no. 12
    
13.
Pradhan P, Pandey AK, Mishra A, Gupta P, Tripathi PK, Menon MB, et al. Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag. bioRxiv 2020;2020.01.30.927871.  Back to cited text no. 13
    
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Available from:https://edition.cnn.com/2020/02/08/opinions/corona virus-bociurkiw/index.html. [Last accessed 2020 May 24].  Back to cited text no. 15
    
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17.
Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020;26:450-2.  Back to cited text no. 17
    
18.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. 2020;94:e00127-20. Published 2020 Mar 17. doi:10.1128/JVI.00127-20.  Back to cited text no. 18
    




 

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