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English is great.
The authors report the possible use of galectin inhibitors for COVID 19 treatment. The rationale is based on structural similarity between the pikes and galectin 3.
The authors haven't addressed the work of David Platt, see section ''validity of findings'' , still, the information is important and the hypothesis is strong.
The authors should strengthen the hypothesis by referencing how does structural similarity between two proteins may lead to mechanisms that inhibitors will work, for example COVID spikes?
The authors must address this statement and include the results from David Platt in their discussion. :
''There is strong evidence that supports the possible use of a galectin inhibitor in COVID-19. According to the Centers for Disease Control and Prevention, the elderly population who have underlying medical conditions, such as diabetes, hypertension, organ fibrosis, or cancer are at a higher risk of getting very sick from this illness. What these people have in common is high lectin type galectin expression. High galectin blood serum concentrations are all associated with these underlying medical conditions which is why clinicians are having such a hard time treating COVID-19 using traditional therapies. Galectins have a tendency to degrade the immune system of people with underlying disease, which leaves them vulnerable against a cytokine storm.
Bioxytran’s new viral inhibitor is expected to restore the adaptive immune system to normal function, which should modulate any existing cytokine storm. In addition, there is preclinical evidence that a galectin inhibitor can bind to the protein spikes of the coronavirus. The company’s medical advisory board has theorized that binding to the virus could stop cell entry and assist in elimination of the virus which would then be attached to the drug and processed out by the liver.
Galectins are also at the center of a number of inflammatory cycles and thereby crucial in the pathogenesis of many chronic diseases such as organ fibrosis and psoriasis. Targeting these inflammatory pathways with an inhibitor could have the potential to quiet the immunological response which ultimately leads to a healing or a reduction in the side effects in many of these potential disease indications. Targeting galectins may have far reaching implications in many diseases thereby having platform technology potential.
“I have been researching galectins and complex carbohydrate modifications for over 35 years, and recent events necessitate an adjustment to our strategy,” said Dr. David Platt, CEO of Bioxytran Inc. “Galectins are part of COVID-19’s recognition system that facilitates viral entry. A few preclinical studies of the coronavirus genus have demonstrated a common galectin fold on the spike protein that is universal to the coronavirus genus. Galectin inhibitors are designed to interfere with this recognition process and prevent viral entry. Galectins are also modulators of the immune response and can be upregulated or downregulated to generate a pro-inflammatory or anti-inflammatory response. Our galectin inhibitor may be able to block viral entry and reduce the T-cell anergy. Our rationale for a viral entry inhibitor is based on extensive scientific evidence. We believe that our drug candidate can eliminate COVID-19. It is an important distinction to make that the viral inhibitor is not an antibody. Although it will be used as an antiretroviral, it should be recognized as an entry or fusion inhibitor that prevents the virus from entering the host cell.”
“The research that links COVID-19 to galectins is very attractive and an eye-opener to novel approaches to fight these deadly viruses,” said Juan Carlos Lopez-Talavera, MD, Ph.D., Consulting Medical Director for Bioxytran Inc. “During the SARS and MERS outbreaks much research was conducted on the composition of the virus with the hope of understanding how the virus works. Some of these studies openly concluded that galectins may represent a therapeutic target and should be investigated further. These outbreaks eventually subsided, and along with them, the motivation to conduct further research and development.”
“Bioxytran is simply connecting the dots by testing its theories with existing galectin inhibitors. The study titled Receptor Recognition Mechanism of Coronaviruses: a Decade of Structural Studies seems to implicate galectins in the pathogenesis of coronaviruses. Hence, galectin may represent an optimal target to treat COVID-19. Reduction of the viral load is a good treatment option, but may do nothing to address the cytokine storm which eventually results in Acute Respiratory Distress Syndrome (ARDS). Our galectin inhibitor can potentially reduce viral entry, help clearing the virus from the blood, and restore homeostasis to the immune system.”
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This manuscript proposed by the authors as a review of the literature in the context of covid-19 is very relevant, as it touches on the current serious problem of the whole world - how to stop the virus invasion in the human body, how to neutralize it, and how to strenghten human immune response. Aspect of structural similarities of the spike proteins of coronaviridae and the human Galectin-3, as well as issue of the search for Gal-3 inhibitors is very intriguing.
The manuscript meets the requirements of the journal, namely: it’s English is clear and professional, introduction is appropriate to the context, the cited literature gives both a General idea of the subject and some recent achievements, the structure conforms to PeerJ standards and discipline norms, the review could be of interest both for specialists in medicine, microbiology and virology and other scientists, the area concerned is in the center of attention of the scientific community and needs new ideas.
The study of literature represented by the authors is in accordance of the aims and scope of the PeerJ, The review organized logically into coherent paragraphs/subsections and are easy reading.
Methods described sufficiently to replicate (unfortunately, the author of the present peer-review could not apply PubMed or Google Scholar browser using the authors’ search terms because the Table S1 that the authors refer to in the text of the articles, was not supplied).
The literature sources are cited adequately. Perhaps not quite convincing is the citation of article (Mao et al., 2020), lines 80-82, where the authors from Chinese Wuhan, among the neurological symptoms, call only cerebrovascular diseases, impaired consciousness, and skeletal muscle injury – which are not specific neurological.
The authors have done a lot of work on comparing the structure and function of lectins, especially Galectin-3, and the spike protein of coronoviruses. They were able to find correlations between the structure of a fragment of the SARS-CoV2 spike protein of the and the structure of galectin-3, between the tropism of the virus to mammalian tissues and the predominant organ damage in viral infection. But there are issues that need to be considered in order to create an objective picture.
The first, only one author (see lines 83-91) found similarity of the spike protein NTD and Galectin-3 molecule. This author discusses only the spatial structure of molecules designed by crystallography methods, although the structure of electric charges and the presence of hydrophobic sites are equally important for intermolecular interaction. I am afraid that the structural correspondence shown in Fig. 1 looks unconvincing considering the three-dimensionality of objects. Besides, direct evidence of functional similarity of molecules is required, for instance the SARS-CoV2 spike protein binding to cell surface gangliosides or specific antibody's cross-reaction, these data were not found by the authors. Perhaps, the authors would have more explicitly pointed out the need for such studies to prove the structural and functional similarity of the molecules.
The second, a series of data indicates the direct participation of Gal-3 and other galectins in the development of an innate immune response to a viral infection, therefore, their inhibition may not stimulate, but suppress antiviral immunity (Vasta GR Roles of Galectins in Infection. Nat Rev Microbiol. 2009 Jun;7(6):424-38. doi: 10.1038/nrmicro2146; Vasta GR Galectins in Host-Pathogen Interactions: Structural, Functional and Evolutionary Aspects Adv Exp Med Biol 2020;1204:169-196. doi: 10.1007/978-981-15-1580-4_7; Li FY, Wang SF, Bernardes ES, Liu FT. Galectins in Host Defense Against Microbial Infections. Adv Exp Med Biol. 2020;1204:141-167. doi: 10.1007/978-981-15-1580-4_6.PMID: 32152946. I would recommend discuss this issue in the text of the paper.
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