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

Abstract

: 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 is 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 has emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs) which facilitates virus entry into the host cells, exists as 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 envelop 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 have 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 the SARS-CoV-2 in particular.

Sensing the interactions between carbohydrate-binding agents and N-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies

“…Potential clinical applicability of antiviral lectins is limited due to associated unfavorable responses such as mitogenicity, hemagglutination and inflammation (Balzarini, 2007a;Gupta et al, 2020). Therefore, we decided to perform the macromolecular docking of BanLec with SARS-CoV-2 S glycoprotein by using wild-type (PDB ID: 3MIT) as well as a mutant (H84T, in which the mitogenic activity of BanLec is separated from the antiviral activity) (PDB ID: 4PIT) of BanLec.…”

Man-Specific Lectins from Plants, Fungi, Algae and Cyanobacteria, as Potential Blockers for SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) Coronaviruses: Biomedical Perspectives

“…A very limited number of potential O -glycosylation sites occupied by GalNAc and T/Tn-antigens have been identified, especially in the SARS-CoV-2 S-glycoprotein [ 12 ]. According to their heavily N -glycosylated character, S-glycoproteins of coronaviruses represent particularly relevant targets for mannose-specific (Man-specific) lectins, a heterogeneous group of proteins involved in the recognition of Man, mannosides, and complex Man-containing glycans, already known for their potential anti-viral and anti-cancer properties [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

Man-Specific, GalNAc/T/Tn-Specific and Neu5Ac-Specific Seaweed Lectins as Glycan Probes for the SARS-CoV-2 (COVID-19) Coronavirus

“…Although lectins remain attractive anti-coronavirus candidates, at present it remains difficult to correctly assess the actual role of these natural compounds in the therapeutic armamentarium, to fight against SARS-CoV-2, the coronavirus responsible for the highly transmissible infectious COVID-19 [103][104][105][106].…”