Covid -19 Glycoprotein can be Modified by Adding Short Oligosaccharide or o-Polysaccharide Derived from E. coli Making Weakness or Lose of ACE-2 Attachment

Introduction

(SARS-CoV-2), the causative pathogen of COVID-19 [1,2], induces fever, severe respiratory illness and pneumonia. SARSCoV- 2 develops a widely glycosylated spike (S) protein that bulges from the viral surface to bind to angiotensin-converting enzyme 2 (ACE2) to mediate host-cell entry [3]. The S protein is tri-meric class I fusion protein, composed of two functional sub-units, responsible for receptor binding (S1 subunit) and membrane fusion (S2 subunit) [1,2]. Remarkably, the surface of the envelope spike is dominated by host-derived glycans with each trimer displaying 66 N-linked glycosylation sites.

There are two sites on SARS-CoV-2 S that are principally oligomannose-type: N234 and N709. The predominant oligomannose- type glycan structure observed across the protein, with the exception of N234, is Man5GlcNAc2, which demon-strates that these sites are largely accessible to α1,2 -manno-sidases but are poor substrates for GlcNAcT-I, which is the gateway enzyme in the formation of hybrid- and complex-type glycans in the Golgi apparatus. The stage at which processing is impeded is a signature related to the density and presentation of glycans on the viral spike. For example, the more densely glycosylated spikes of HIV- 1 Env and Lassa virus GPC exhibit numerous sites dominated by Man9GlcNAc2 [3-4].

Commensal bacteria and their products can indirectly protect against Influenza A virus (IAV) infection by interacting with the host’s immune system in the absence of commensal bacteria, mice suffered from impaired type I/II interferon responses, CD4/CD8 T cell responses, and antibody production to IAV infection [6,7]. Moreover, mice pretreated with bacterial lipopolysaccharide (LPS), a product present on the exterior surface and shed by all Gramnegative bacteria, triggered a Toll-like receptor 4 (TLR4)-mediated antiviral response to protect the hosts from lethal infection with IAV [8,9]. In contrast, LPS was found to bind directly to the capsid protein of poliovirus, increasing cell attachment and the ability of the virions to remain infectious at elevated temperatures [10]. Additionally, LPS binding to mouse mammary tumor virus (MMTV) resulted in increased immune evasion and transmission of the virus [5]. In the case of influenza, it is unclear whether commensal bacteria and LPS are interacting directly with IAV in addition to their indirect effects on the immune system.

Conclusion

In these study we make fragments either in laboratory or taken from LPS o- side chain containing 13 oligosaccharides units then firstly, performing in vitro study to detect if these oligosaccharide inhibits virus entry on specific TC cells

The second trial applied on monkey as in vivo study to detect that if block virus entry and study the toxicity if present.

References

• Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367(6483): 1260-1263.
• Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, et al (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181(1): 281-292.
• Struwe WB, Chertova E, Allen JD, Seabright GE, Watanabe Y, et al (2018) Site-specific glycosylation of virion-derived HIV-1 Env is mimicked by a soluble trimeric immunogen. Cell Rep. 24(8): 1958-1966.
• Watanabe Y, Raghwani J, Allen JD, Seabright GE, Li S, et al (2018) Structure of the Lassa virus glycan shield provides a model for immunological resistance. Proc. Natl. Acad. Sci. U.S.A. 115, 7320-7325.
• Kane M, Case LK, Kopaskie K, Kozlova A, MacDearmid C, et al(2011) Successful transmission of a retrovirus depends on the commensal microbiota. Science 334(6053): 245-249.
• Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, et al (2011) Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci 108: 5354-5359.
• Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, et al (2012) Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37(1): 158-170.
• Shinya K, Ito M, Makino A, Tanaka M, Miyake K, Eisfeld AJ, Kawaoka Y. 2012. The TLR4-TRIF pathway protects against H5N1 influenza virus infection. J Virol 86(1): 19-24.
• Shinya K, Okamura T, Sueta S, Kasai N, Tanaka M, et al (2011) Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses. Virol J 8: 97.
• Robinson CM, Jesudhasan PR, Pfeiffer JK (2014) Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus. Cell Host Microbe15(1): 36-46.