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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The Qβ VLPs were used to display high-mannose glycans that were identified on the HIV-1 envelope glycoprotein, gp120, as a target for neutralizing antibody 2G12, the first HIV-1 antiglycan neutralizing antibody described (Doores et al. 2013). This study contributed markedly to the putative HIV carbohydrate vaccine design strategies. The Qβ VLP-based glycovaccines were reviewed by Restuccia et al. (2016).
Heterocyclic Drugs from Plants
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Valeria Garcia, Felipe Gonzalez
Flavonoids, frequently found in fruits, vegetables, nuts, medicinal plants, and wine have varying phenolic structures. These are commonly known owing to their multifunctional pharmacological and nutraceutical benefits. Flavonoids have shown anti-inflammatory, anti-HIV, anti-oxidative, anti-carcinogenic, anti-mutagenic, and some other curative/preventive activities (Panche et al., 2016). Studies concerning flavonoids were done to support the efficacy of flavonoids in inhibiting both HIV-1& -2 (Mahmood et al., 1993) up to a certain level. The investigational flavonoids interacted irreversibly with envelope glycoprotein gp120 to deactivate viral infectivity and subsequently reduced infection (Mahmood et al., 1993). GP120 is a biomolecule found in HIV-1, a glycoprotein that participates in constructing the viral outer layer (Yoon et al., 2010). This molecule facilitates the entry of HIV into the host cell and helps to generate the infectious path of HIV. However, gp120 might also interact with CD4 cells. The glycoprotein showed an ease in endorsing the viral continuance by influencing the CD4 cells.
VLP Vaccines
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The Qβ VLPs were used to display high-mannose glycans that were identified on the HIV-1 envelope glycoprotein, gp120, as a target for neutralizing antibody 2G12, the first HIV-1 antiglycan neutralizing antibody described (Doores et al. 2013). This study contributed markedly to the putative HIV carbohydrate vaccine design strategies. The Qβ VLP-based glycovaccines were reviewed by Restuccia et al. (2016). Furthermore, a third-generation anti-glycane vaccine was generated against two Streptococcus pneumoniae pathogenic serotypes, where long-term protective immunity in mice was elicited with exquisite specificity (Polonskaya et al. 2017). Furthermore, the α-Gal trisaccharide epitope was identified on the surface of the protozoan parasites Leishmania infantum and L. amazonensis, the etiological agents of visceral and cutaneous leishmaniasis, respectively, and displayed on the Qβ VLPs (Moura et al. 2017). The putative vaccine demonstrated high efficiency in a C57BL/6 α-galactosyltransferase knockout mouse model and protected animals against Leishmania challenge, eliminating the infection and proliferation of parasites in the liver and spleen as probed by qPCR. The α-Gal epitope might therefore be considered as a vaccine candidate to block human cutaneous and visceral leishmaniasis (Moura et al. 2017). A detailed protocol for the conjugation of a prototypical tumor-associated carbohydrate antigen (TACA), the Tn antigen, to the Qβ VLPs was published by Sungsuwan et al. (2017).
Functional mimetic of the G-protein coupled receptor CXCR4 on a soluble antibody scaffold
Published in mAbs, 2019
Adem C. Koksal, Meghan E. Pennini, Marcello Marelli, Xiaodong Xiao, William F. Dall’Acqua
Antibody CDRs are highly variable, and coupled with framework mutations can have a significant effect on antibody folding, stability, and antigen binding.20 Thus, we mined the protein structure database, both manually and using NCBI/Blast, to identify antibodies with properties amenable to host the CXCR4 ECLs. We determined that the CDRH3 of the broadly neutralizing HIV antibody b12 had sequence homology to the ECL2 of CXCR4 (Figure S1). We posited that this sequence similarity may be advantageous because this antibody would be amenable to ECL2 grafting with the least disruption to its native structure. In addition, its full IgG structure has been crystallographically characterized both alone and in complex with its antigen, the HIV-1 envelope glycoprotein gp120.21,22 Given that the structural information for CXCR4 is also known,12 we set out to identify the possibility of grafting the CXCR4 N-terminus and ECLs onto b12 at its CDRs.
Envelope proteins as antiviral drug target
Published in Journal of Drug Targeting, 2020
Jyoti Verma, Naidu Subbarao, Maitreyi S. Rajala
The virion particles interact with specific receptor present at the host cell surface. The interaction occurs between a specific region (receptor binding region) in the envelope protein and the host cell receptor initiating internalisation of the virus particle into the cell. Various studies report the development of small molecule inhibitors against the attachment of different viruses to their receptors. A group at Bristol-Myers Squibb Pharmaceutical Research Institute identified compounds directly binding to the HIV envelope glycoprotein gp120. Their study reports that the compounds BMS-378806, BMS-488043 and their analogs block the interaction between gp120 and CD4 receptor [33]. Also, NBD-556, NBD-09027, JRC-II-191 and their derivatives developed by Debnath et al. [34] inhibited gp120 interaction with CD4 at a low micromolar range. Various natural products and their derivatives such as curcumin, epigallocatechin gallate (EGCG), AL-1 and saponins target hemagglutinin (HA) protein of influenza virus to block its binding to the host cell receptor. Other natural compounds namely, Rutin, Quercetin, Xylopine and Theaflavins are also known to interact with HA of Influenza virus [35,36]. Another compound Neoechinulin B was identified as an inhibitor of HA, which disrupts its interaction with the host cell receptor [37]. The EC50 (concentration of a drug that gives half-maximal response) values of Neoechinulin B varies for different strains of Influenza virus and Nitazoxanide is reported as a broad-spectrum antiviral drug blocking the maturation of HA [38]. Few studies have reported inhibiting the Spike (S) protein of coronaviruses by small molecules. A compound, SSAA09E2 prevents the interaction of SARS-CoV S protein with its receptor ACE2 [39]. A study carried out based on a concept of chemical genetics has reported 18 small molecules with anti SARS CoV activity targeting S protein-ACE2 mediated viral entry [40]. Emodin, an anthraquinone compound identified from Chinese medicinal herb has the ability to inhibit the SARS-CoV S protein from binding to its receptor ACE2 [41].