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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

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Science  13 Mar 2020:
Vol. 367, Issue 6483, pp. 1260-1263
DOI: 10.1126/science.abb2507

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  • Re: pH boosters/regulator as a potential candidate in managing COVID19
    • Rajesh Kumar, Associate Professor, Discipline of Physics, Indian Institute of Technology Indore
    • Other Contributors:
      • Hem C. Jha, Assistant Professor, Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore

    Thanks to Wrapp et al [1] for coming up with a clear picture of the 2019-nCoV spike structure. This work along with some others (e.g, https://www.ncbi.nlm.nih.gov/books/NBK554776/) very clearly shows that the viral membrane consists of proteins (the S-protein) which are fatty in nature. This fatty nature of the virus spike suggests that its survival on a basic media will be highly compromised. In other words, pH booster like pantoprazole can be helpful in managing the life threatening situation in critically sick patients suffering from COVID-19. W. Londong in his work [2] very clearly shows how administration of pantoprazole helps in increasing 24-h intragastric pH value on humans.

    If the blood pH values of COVID19 patients are increased (> 7.5) beyond the value of the same at the time of n-CoV infection, its basic nature will destroy the fatty viral membrane to eventually kill the virus. This may prove life saving in critically sick patients. In view of the above adopting following steps can help in not only managing the crisis well but also may prove to be life saving:
    (a) To administer pH boosters (e.g, pantoprazole, ranitidine, omeprazole etc.) to moderate to critically sick COVID19 patients with an understanding that it may induce alkalosis that can be managed relatively easier as it does not carry consequences more severe than COVID19.
    (b) Local administration of pH boosters, similar...

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    Competing Interests: None declared.
  • RE: Comments on “Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation”
    • Sheng Chen, Professor, Department of Infectious Diseases and Public Health, City University of Hong Kong
    • Other Contributors:
      • Edward Wai-Chi Chan, State Key Lab of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University

    Comments on “Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation”

    Sheng Chen 1* and Edward Wai-Chi Chan2

    1Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong

    2State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;

    *Corresponding author: Sheng Chen, City University of Hong Kong, Kowloon, Hong Kong;
    Email: shechen@cityu.edu.hk

    Keywords: SARS-CoV-2, ACE2, spike protein, conformation, receptor binding


    Abstract
    Wrapp et al. (Reports, February 19, 2020) reported the structure of the spike protein (S) of the novel coronavirus, SARS-CoV-2, in the prefusion conformation and concluded that the protein could bind to the human cell receptor ACE2 with an affinity 10~20-fold higher than that of SARS-CoV-1. However, this finding is not consistent with current results of protein structure studies in which only two interaction sites between SARS-CoV-2 and ACE2 were identified, whereas five were observed in the case of SARS-CoV-1. These structural data, which suggest that binding of SARS-CoV-2 to ACE2 is actually much weaker, are more consistent with the longer incubation period and relatively low pathogenicity of this new coronavirus. Th...

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    Competing Interests: None declared.
  • RE: Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

    Gender-specific Coronavirus-infections in the light of evolution

    In their Report “Cryo-EM structure of the 2019-nCoV” (Science 367, p. 1260–1263; 2020), D. Wrapp et al. write that “The novel coronavirus 2019-nCoV has recently emerged as a human pathogen in the city of Wuhan in China’s Hubei province, causing fever, severe respiratory illness, and pneumonia.” In addition, the authors refer to the rising number of deaths since the official outbreak on December 29, 2019.
    However, with respect to mortality, this disease, recently named “Covid-19”, displays a strong gender-specific occurrence that may be explained in the light of evolution. Four decades ago, A. D. Pickering and P. Christie published a remarkable article entitled “Sexual differences in the incidence and severity of ectoparasitic infestation of the brown trout, Salmo trutta L.” (1). The authors reported that adult males of this fish species are more frequently (and severely) infested by a number of parasites than females of the same age. Remarkably, juvenile fish of both genders were found to be less attacked compared to sexually mature males (1). Numerous papers that were subsequently published “in the wake of Pickering & Christie 1980” have documented that there are gender-specific (or “sex-based”) differences in immunological responses, both to foreign and self-antigens. As a result, in 2009, M. Zuk (2) labelled males as “the sicker sex”.
    In two recent Review Articles entitled “Sex dif...

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    Competing Interests: None declared.
  • RE: Can you test Nano-silver as a therapeutic?

    Dear Sirs: Great work. Very impressive.

    I would like to call your attention to a 2010 study that details how nano silver (aka colloidal silver, aka CS) blocks the attachment of HIV-1 to himan cells. As you know, there is some similarity in the attachment characteristics with COVID-19.

    I would suggest you do in vitro testing of 120 ppm CS, as this strength is the most potent, and its readily available on Amazon in the US. Colloidal silver has been used for decades for its antibiotic and antiviral properties, and is inexpensive and easy to manufacture. And to be clear, I am not talking about silver proteins, as that is a different agent altogether, although also worthy of testing.

    It may be the answer you seek. As the study below indicates, it blocked attachment of HIV-1, not just initially, but for several hours after dosing. Also, it is easily administered orally or via a nebulizer.

    One last thought: we have no immunity against this virus, but it had no "immunity" against nano silver.

    2010 Study article:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818642/

    Also this 2005 study:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1190212/

    Competing Interests: None declared.
  • Unfractionated Heparin and Penicillin should contain 2019-nCoV

    Dear Sir,

    the clinical diagnosis of pneumonia is most often not confirmed by the pathologists.
    Intravascular coagulation is the main actor of innate immunity.
    Virus opens the door, streptococci overwhelm the functions.
    This is lesson from the 1918 Pandemic: 95 % of mortality is induced by bacterial coinfection.
    So penicillin and unfractionated heparin should be discussed as prevention of disseminated intravascular coagulation and bacterial superinfection.

    Competing Interests: None declared.

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