A novel plant lectin, NTL-125, interferes with SARS-CoV-2 interaction with hACE2

Sarkar, Anindya; Paul, Sathi; Singh, Charandeep; Chowdhury, Nilkanta; Nag, Papri; Das, Swarnava; Kumar, S. Suresh; Sharma, Anshul; Das, Deepjyoti Kumar; Dutta, Dipak; Thakur, Krishan Gopal; Bagchi, Angshuman; Shriti, Surbhi; Das, Kali Pada; Ringe, Rajesh P.; Das, Sampa

doi:10.1016/j.virusres.2022.198768

Cited by 12 publications

(17 citation statements)

References 65 publications

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“…The NTL-125, another lectin, was investigated for its high affinity binding to the RBD of several variations. Such binding comes about through the αhelical tail of the protein which interacts with glycan moieties and increases the binding strength [75]. In light of our findings, Smo99732 appears to be a promising candidate for carbohydrate-protein interactions with wide-type spike glycoproteins, given its complex stability, low free energy compared to other S. moellendorffii Hevein-like lectins, and capacity for improved protein-protein interactions with mutant variants' RBMs.…”

Section: Discussionmentioning

confidence: 76%

Genome-Wide Mining of <em>Selaginella moellendorffii</em> for Hevein-Like Lectins and Their Potential Molecular Mimicry with SARS-CoV2 Spike Glycoprotein

Alsolami¹,

Dirar²,

Konozy³

et al. 2023

Preprint

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Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization and their expressional profile in different tissues was studied. These in-silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

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Section: Discussionmentioning

confidence: 76%

Genome-Wide Mining of <em>Selaginella moellendorffii</em> for Hevein-Like Lectins and Their Potential Molecular Mimicry with SARS-CoV2 Spike Glycoprotein

Alsolami¹,

Dirar²,

Konozy³

et al. 2023

Preprint

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“…The broad-spectrum antivirals might inhibit the enveloped virus membrane fusion to exhibit efficacy. Most reports to design a fusion inhibitor 44 are based on targeting the receptor binding domain or fusion domain with the peptides, 15,18,[45][46][47][48][49][50] small molecules, 51,52 lectins, [53][54][55] antibodies, 56 etc. However, the scope for targeting the fusion machinery of a specific virus is limited to that particular infection and hence can not be used against multiple viruses.…”

Section: Resultsmentioning

confidence: 99%

De novo design of lipopeptide-based fusion inhibitor as potential broad-spectrum antiviral agent

Tarafdar

Sardar

Bhowmick

et al. 2023

Preprint

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The recent surge in emerging viral infections warrants the need to design broad-spectrum antivirals. We aimed to develop a lead molecule that targets the membrane to block fusion, an obligate step of enveloped virus infection. The approach is based on the Coronin-1 protein of Mycobacterium, which presumably inhibits the phagosome-lysosome fusion, and a unique Trp-Asp (WD) sequence is placed at the distorted -meander motif. We have designed a WD-based branched lipopeptide that supports C=OHN hydrogen-bonding, the tryptophan-tryptophan - stacking, and the intermolecular H-bonding between COO and CO2H groups. These cooperative interactions are expected to create a -sheet-like supramolecular assembly at the membrane surface, which increases the interfacial order, and decreases the water penetration. Myr-D(WD)2 was shown to block artificial membrane fusion completely. We demonstrated that the Myr-D(WD)2 supramolecular organization can restrict the infection from H1N1, H9N2, murine coronavirus, and human coronavirus (HCoV-OC43). Together, the present study provided an evidence-based broad-spectrum antiviral potential of a designed small lipopeptide.

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“…They act as the primary participants in cis-infection and trans-infection of virus-susceptible cells. Via glycotope receptors, highly pathogenic viruses invade host multiple organs and lead to systemic infection. Collectively, these findings identify a lectin-dependent pathway that enhances receptor-dependent infection by enveloped viruses and reveals distinct mechanisms of evading and suppressing the immune system (Refs 10–12). Finally, for the therapeutic purposes or prevention of viral infection, we should find general glycomimetic ligands or lectins that block the virus interaction with lectin receptors (Refs 12,13,89). For the prognosis role, we should consider individual glycotopes and lectin-receptors affected by sex, age and physiological conditions (Refs 52,57–61).…”

Section: Discussionmentioning

confidence: 99%

“…Finally, for the therapeutic purposes or prevention of viral infection, we should find general glycomimetic ligands or lectins that block the virus interaction with lectin receptors (Refs 12,13,89).…”

Section: Discussionmentioning

confidence: 99%

Dual role of Glycoconjugates and Binding Receptors in pathogenesis of Enveloped Viruses (by main focusing on two recent pandemics)

Pourrajab

Zare-Khormizi

2023

Expert Rev. Mol. Med.

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A period of about a decade has been estimated to pass for the emergence of a new infectious strain of a virus that may lead to the occurrence of a pandemic one. It is now suggested that the variants of the 1918 H1N1 and coronavirus disease-19 pandemics could have existed in humans after the initial cross-species introduction to humans and underwent multiple low-level seasonal epidemics before the occurrence of their outbreaks. They share similarities in the continuation, widespreadness due to high transmissibility, high fatality rate and clinical symptoms. They are assumed to share a similar principle of a zoonotic source and a cross-species pathway for transmission. They show some similarities in their pathogenesis with other enveloped viruses: Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), human immunodeficiency virus, Ebola, Lassa and measles viruses. The highly pathogenic nature of these viruses and their genetic variants may depend on their binding affinity for host cell receptors, whereby they efficiently circumvent or block host cell immune responses triggered by cytokines (interferon). High transmission rates and viral pathogenicity are attributed to glycan moieties that facilitate virus binding to host multiple receptors and cell entry, thereby helping viruses to evade immune recognition and response. Also, mucosa glycotopes are a matter of concern that play as primary sites for virus attachment and body entry. Finding general lectins or ligands that block the viral–host receptors interaction or identifying individual glycotopes is the therapeutic and prognosis topic that demands the main focus.

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A novel plant lectin, NTL-125, interferes with SARS-CoV-2 interaction with hACE2

Cited by 12 publications

References 65 publications

Genome-Wide Mining of <em>Selaginella moellendorffii</em> for Hevein-Like Lectins and Their Potential Molecular Mimicry with SARS-CoV2 Spike Glycoprotein

Genome-Wide Mining of <em>Selaginella moellendorffii</em> for Hevein-Like Lectins and Their Potential Molecular Mimicry with SARS-CoV2 Spike Glycoprotein

De novo design of lipopeptide-based fusion inhibitor as potential broad-spectrum antiviral agent

Dual role of Glycoconjugates and Binding Receptors in pathogenesis of Enveloped Viruses (by main focusing on two recent pandemics)

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