Synthetic Carbohydrate Binding Agents (CBAs) Prevent SARS-CoV-2 Entry by Inhibiting Binding of the Spike Protein to the ACE2 Receptor

2021 ◽  
Author(s):  
Oscar Francesconi ◽  
Lorena Donnici ◽  
Marco Fragai ◽  
Elisa Pesce ◽  
Mauro Bombaci ◽  
...  
Keyword(s):  
Spike Protein ◽  
Carbohydrate Binding ◽  
Binding Agents ◽  
Synthetic Carbohydrate

Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1085-1096 ◽  
Author(s):  
Rajesh Kumar Gupta ◽  
Girish R. Apte ◽  
Kiran Bharat Lokhande ◽  
Satyendra Mishra ◽  
Jayanta K. Pal
Keyword(s):  
Vaccine Development ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Atypical Pneumonia ◽  
The Novel ◽  
High Infection ◽  
Binding Agents ◽  
Current Scenario ◽  
Antiviral Activities ◽  
Novel Drug

: With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.

scholarly journals Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents

2013 ◽  
Vol 68 (9) ◽  
pp. 2026-2037 ◽  
Author(s):  
M. I. Petrova ◽  
L. Mathys ◽  
S. Lebeer ◽  
S. Noppen ◽  
E. J. M. Van Damme ◽  
...  
Keyword(s):  
Carbohydrate Binding ◽  
Binding Agents ◽  
Hiv 1

scholarly journals Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

2014 ◽  
Vol 10 ◽  
pp. 1354-1364 ◽  
Author(s):  
Melanie Rauschenberg ◽  
Eva-Corrina Fritz ◽  
Christian Schulz ◽  
Tobias Kaufmann ◽  
Bart Jan Ravoo
Keyword(s):  
Molecular Recognition ◽  
Self Assembled Monolayers ◽  
Carbohydrate Binding ◽  
Air Oxidation ◽  
Acetylneuraminic Acid ◽  
Physiological Processes ◽  
Wide Range ◽  
Assembled Monolayers ◽  
Synthetic Carbohydrate ◽  
Derivatives Of

The molecular recognition of carbohydrates and proteins mediates a wide range of physiological processes and the development of synthetic carbohydrate receptors (“synthetic lectins”) constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by our previous work, we prepared a fluorescently labeled synthetic lectin consisting of a cyclic dimer of the tripeptide Cys-His-Cys, which forms spontaneously by air oxidation of the monomer. Amine-tethered derivatives of N-acetylneuraminic acid (NANA), β-D-galactose, β-D-glucose and α-D-mannose were microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut agglutinin. It was found that the printed carbohydrates retain their characteristic selectivity towards the synthetic and natural lectins and that the recognition of synthetic and natural lectins is strictly orthogonal.

Capture and transmission of HIV-1 by the C-type lectin L-SIGN (DC-SIGNR) is inhibited by carbohydrate-binding agents and polyanions

2009 ◽  
Vol 83 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Joeri Auwerx ◽  
Katrien O. François ◽  
Els Vanstreels ◽  
Kristel Van Laethem ◽  
Dirk Daelemans ◽  
...  
Keyword(s):  
Carbohydrate Binding ◽  
Binding Agents ◽  
Hiv 1

scholarly journals Antiviral Activity of Carbohydrate Binding Agents (CBAS) and the Role of DC-SIGN in Dengue Virus and HIV Infection

2009 ◽  
Vol 82 (2) ◽  
pp. A22
Author(s):  
Marijke Alen ◽  
Suzanne J.F. Kaptein ◽  
Tine De Burghgraeve ◽  
Johan Neyts ◽  
Jan Balzarini ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Hiv Infection ◽  
Carbohydrate Binding ◽  
Binding Agents

scholarly journals Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin

2015 ◽  
Vol 96 (12) ◽  
pp. 3660-3666 ◽  
Author(s):  
Bodan Hu ◽  
Tao Du ◽  
Chang Li ◽  
Sukun Luo ◽  
Yalan Liu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Carbohydrate Binding ◽  
Immunodeficiency Virus ◽  
Binding Agents ◽  
Galanthus Nivalis ◽  
Hiv 1 ◽  
Microbicide Candidate

Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 ± 0.0003 to >10 nM for GRFT, from 0.6 ± 0.2 to 28.9 ± 2.9 nM for CV-N and from 1.3 ± 0.2 to >500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.

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