SARS-CoV-2 Virology and Vaccines/Therapies

Compiled by Melissa Baringa for Science for the People
Last updated: April 24, 2020

Virology: Origins of SARS-CoV-2

This topic has been polarized and controversial internationally since the first COVID-19 cases. There have been charges of the virus’ origins at a Wuhan seafood market while others argue that this was a crowded market, where human-to-human transmission would be likely and the spread may have occurred at the market in a few cases but originated from other sources, and the origin has not yet been proved. The high homology to the bat virus (Bat-RaTG13), ~96% identical to SARS-CoV-2, has led to the theory of the bat as a host and another, potential intermediate host. Some have argued the virus’ origins are not important to discuss at this moment as are cures and drugs however, there have been ongoing allegations and rebuttals regarding this subject and lab origin arguments have even been considered in ‘mainstream’ scientific journals, such as in the journal Nature, a discussion not normally entertained in these journals, which is remarkable.

This topic draws on both scientific articles that discuss and make scientific arguments regarding the origins of SARS-CoV-2 as well as those discussing the history of countries engaging in biological research for military purposes to understand these current allegations. This includes those articles that SfTP has previously published, i.e., SfTP in 1984, Volume 16, No. 3, that discusses ‘offensive’ research as a possible outcome of ‘defensive’ research (Ruttman, R. “’Strictly Anti-Human’ Chemical and Biological Warfare”, Science for the People, 1984, Volume 16, No. 3).

Many of the scientific articles curated here document methods used to increase the pathogenicity of bat coronaviruses, or to expand their tropism, i.e., change them so that they can infect human cells. The reason given for this research is that this allows for the prediction of how a pandemic could occur. However, these types of studies raise bioethical issues as these approaches create more pathogenic viruses under the auspices of predicting pandemics. This argument is remarkably similar to those that have been used in the past to justify ‘defensive’ biologic weapons research, which is virtually indistinguishable in the experiments and information obtained with ‘offensive’ biologic weapons research. It is important for SfTP to provide resources to consider a variety of articles and perspectives in this matter as there is a strong argument that an origin has not been proved nor convincingly argued. While perhaps not an urgent matter as those regarding therapies and vaccines, these articles in this space would include those from diverse viewpoints in order to consider a wide range of arguments and resources.

Resources

1. K. G. Andersen et al. The proximal origin of SARS-CoV-2. Nature Medicine. Published online March 17, 2020. doi: 10.1038/s41591-020-0820-9.
2. How did covid-19 begin? Its initial origin story is shaky.: The U.S. and China need to find the answer together. The Washington Post (Online), Washington, D.C.: WP Company LLC d/b/a The Washington Post. Apr 2, 2020.
3. This LA Times article reports that USAID funded a program called “PREDICT” whose goal was to train foreign scientists in collaboration with U.S. scientists to identify “1,200 different viruses that had the potential to erupt into pandemics, including more than 160 novel coronaviruses.” It had trained and supported foreign scientists including Chinese scientists at the Wuhan laboratories that identified SARS-COV-2. PREDICT had gone on for over 10 years and was suspended in September 2019 by the Trump administration as discussed in this article.
4. This article appeared in Nature Medicine in 2015, A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. The research was funded by the USAID-EPT-PREDICT, EcoHealth Alliance, National Natural Science Foundation of China, and the NIH. This article reports on research that takes a circulating bat coronavirus spike protein and puts it into a SARS-CoV backbone that has been adapted to mice. The authors study the chimeric virus, finding the infection is refractory to neutralizing antibodies and vaccines produced for the SARS
5. A paper by Pradhan et al. (by Scientists from New Delhi, India), Uncanny similarity of unique inserts in the 2019-nCoV2019 spike protein to HIV-1 gp120 and Gag was published in BioRxiv first posted online on Jan. 31, 2020 and was retracted. This paper looked at four insertions in the SARS-CoV-2 genome not found in other coronaviruses and performed sequence homology analysis using pre-existing databases (the National Center Biotechnology Information BLAST program) to align sequences. The authors found that homology to HIV strains came up in their results. The paper did not argue for a lab origin, per se, but presented these data and this analysis.
6. In response to the Pradhan et al. article, other counterarguments and analyses were published. These included various arguments against the conclusions of this paper, one report was “HIV-1 did not contribute to the 2019-nCoV genome” and another argued there was no evidence for HIV-1 like sequences in SARS-CoV-2.
7. The furin domain in SARS-CoV-2 is not present in other beta coronaviruses and differs from the bat coronavirus (Bat-RaTG13) that has the greatest homology to SARS-CoV-2 (~96%). How or where this domain was acquired is not clear and is an area under scientific investigation.
8. Interestingly, a few articles have appeared between April 12-14^th, 2020 in the mainstream press including in the New York Times, National Review and the Washington Post, stating the SARS-CoV-2 origin has not been proved and is probably natural, but this is “not certain”. These articles report, in 2018, that U.S. State Department diplomats collaborating with Wuhan labs that were working with modifying bat coronaviruses, commented on concerns of biosafety in the lab and fear of possible dangerous outcomes. In fact, these articles cited, above, as one such bat coronavirus- concerning study.
9. The President of EcoHealth Alliance (Peter Daszak), sharing his opinion of how the coronavirus could not have been lab engineered. From our archived sources, what is notable is that EcoHealth Alliance co-funded, with the USAID PREDICT program, referenced above, research that included the engineering of chimeric (spliced) bat coronavirus components (bat coronavirus spike proteins) into the SARS-CoV virus at the Wuhan labs, not simply collecting samples to analyze from natural settings. USAID PREDICT funded projects also included studies to see how alterations in bat coronaviruses could render the bat virus able to infect human cells. For example, one such study showed treatment with trypsin, a protease, could overcome the bat coronavirus restriction to infecting human cells. While the USAID PREDICT and EcoHealth Alliance funded projects aimed to ‘predict’ bat-to-human zoonotic infections, they also included projects that manipulated bat and human viruses to determine what changes would result in expanded host range and tropism.
10. This is a comprehensive analysis from the investigative journalist, Sam Husseini, summarizing both sides of the debate of natural and lab origin of SARS-CoV-2. This article proposes that the critical question is not whether SARS-CoV-2 has a natural or lab origin, but that prior laboratory research that has been done to increase the pathology of infectious agents, including coronaviruses, exposes “the threat of a biowarfare arms race”, according to Husseini. This article was published in Salon.com on April 24, 2020.
11. These two articles are related to the attack on U.S. basic scientists who collaborate with Chinese scientists, yet U.S. funding agencies, in many cases, provide funding and support for many U.S. – Chinese scientist collaborations, as described in programs such as PREDICT program, described above. Although this is not about the virology per se, these attacks appear to be a direct response to the SARS-CoV-2 pandemic, and therefore are mentioned here. This article, “Universities are forging ties with the FBI as US cracks down on foreign influence” appeared in Nature 12 March 2020. This article appeared in Nature 3 Feb 2020. “Harvard chemistry chief’s arrest over China links shocks researchers
12. “The Long History of Accidental Laboratory Releases of Potential Pandemic Pathogens Is Being Ignored In the COVID-19 Media Coverage”, is a comprehensive article by Sam Husseini, posted May 5, 2020 on independent science news. This provides an analysis of the history of biohazards associated with high-containment biological agents, particularly those associated with historic bioweapons research. Also considered is how the current Chinese SARS-CoV-2 lab origin arguments deflect US involvement. As stated in this article,”If current dynamics continue, the rightwing will use the issue of biolabs to demonize China, and perhaps other states, without there being any serious scrutiny applied to bioweapons work by the U.S. and its allies (Israel has not even signed the Biological Weapons Convention)”.
13. “The Case Is Building That COVID-19 Had a Lab Origin” by Jonathan Latham and Allison Wilson on June 2, 2020 in Independent Science News. This article surveys arguments for a natural or lab origin of SARS-CoV-2.

Vaccines and Therapeutic Drugs for SARS-CoV-2

This topic will consider the various proposed therapies and vaccines under investigation for SARS-CoV-2. This would include basic virology articles with links and resources that may provide useful information. Given a lot of press coverage has discussed a Moderna/NIH vaccine currently in Phase I clinical trials, which uses RNA of the virus, articles considering this vaccine are included. Others are using synthetic biology to make nanoparticles with the SARS-CoV-2 spike (S) protein. There has been discussion of “digital immunity ID” or “digital [vaccination] certificates” by Bill Gates, backed by Microsoft among others https://id2020.org/alliance. A lot of attention has been drawn to hydroxychloroquine (HCQ) in combination with azithromycin as a potential intervention or prophylaxis. This was initially observed to be beneficial to a group of patients with SARS-CoV-2 in China and in France but has not been studied in a controlled clinical trial and whose efficacy has not been proved. HCQ is now being tested in multiple clinical trials around the world. Now that clinical trials have begun, two trials have shown cardiovascular adverse events and were stopped. These articles also will include aspects of Citizen Science and researchers sequencing SARS-CoV-2 strains and using collaborative international platforms such as Nextstrain and other resources to track viral mutation rates and spread by sharing these interactive tools.

A key question in this arena is “Who stands to benefit from these initiatives?” The Bill and Melinda Gates foundation, and specifically, Bill Gates, has been clear that he supports both a mandatory vaccine and “digital [microchip] immunity IDs”. These digital ID proponents suggest implantable IDs that include an individual’s vaccination and infection test status will be advantageous for ‘return to work’. Alongside this proposition has been the discussion of a mandatory SARS-CoV-2 vaccination. Disentangling the obvious interest of those vaccine- and drug-producing companies who stand to benefit, with those of the public’s health, are also types of resources to be included in this space.

Resources

1. Overview of current clinical trials for drugs and vaccines being tested for SARS-CoV-2 from the Danish Medicine Agency.
2. This is an excellent resource and database to search current clinical trials. https://clinicaltrials.gov is a searchable resource for clinical trials. Using SARS-Cov-2 or COVID-19, you can search current clinical trials for COVID-19.
3. Articles on RNA/DNA vaccines discussing the Moderna/NIH vaccine approach: https://crosscut.com/2020/03/meet-seattle-scientist-racing-toward-coronavirus-vaccine.
4. Using Synthetic Biology, Nanoparticles, and a DNA Vaccine from the Gates Foundation initiative.
5. Bill Gates proposes “digital immunity ID”. Gates, in a recent TED talk, discusses some of this proposal (~34:00) https://www.youtube.com/watch?v=Xe8fIjxicoo.
6. Summary of state of knowledge of hydroxychloroquine (HCQ) for SARS-CoV-2 infections. Serious side effects reported with at least two HCQ small-scale clinical trials – one in France and one in Brazil.
7. Members of congress and other government officials are advocating for SARS-CoV-2 vaccine trial participants to agree to SARS-CoV-2 infection to test vaccine efficacy.

Virology/Citizen Science

Data analysis platforms such as the viral sequence analysis program, nextstrain, allow individuals to submit viral sequences and view their relationships to other deposited viral sequences, in real-time. This method decentralizes the data, allowing the potential for greater transparency in data analysis than with centralized data collection and analysis. For example, the mutation rates of SARS-CoV-2 can be estimated from the submitted sequences from independent international contributors and the relationships between the viral strains determined at the time of submission, which are publicly available.

Early analysis of a large number of COVID-19 clinical cases in Wuhan, China provided a starting point from which we can understand the disease course and clinical outcomes of SARS-CoV-2 infections and papers summarizing these early findings are included here. Other aspects of how virology data collection is or can be being decentralized and is promoting community analysis of data will be included in this section.

Resources

1. Trevor Bedford Lab. Real-time tracking of pathogen evolution using https://nextstrain.org/, showing mutation rates and projections by the international sharing of SARS-CoV-2 sequences. https://nextstrain.org/narratives/trees-background/.
2. The citation for the nextstrain program is Hadfield et al., Nextstrain: real-time tracking of pathogen evolution, Bioinformatics (2018).
3. This article provides one of the early comprehensive analyses of clinical features of COVID-19 in Wuhan, China. A Feb. 28^th comprehensive clinical summary and outcomes of cases in China. Guan et al., 2020. New England Journal of Medicine.
4. Modeling approaches based on viral sequencing from March-April 2020.