Multivalent oleanolic acid human serum albumin conjugate as nonglycosylated neomucin for influenza virus capture and entry inhibition

Yang, Yang; He, Hao-Jie; Chang, Hao Teng; Yu, Yao; Yang, Mei-Bing; He, Yan; Fan, Zhen‐Chuan; Iyer, Suri S.; Yu, Peng

doi:10.1016/j.ejmech.2017.10.070

Cited by 29 publications

(18 citation statements)

References 43 publications

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“…Of interest, some of these agents have been reported for the potential use as anti-HIV agents (Rezanka et al, 2009), and oleanolic acid has been reported as a broad spectrum entry inhibitor of influenza viruses (Yang et al, 2018). On the other side, betulinic acid has been demonstrated to be useful in reducing inflammation and pulmonary edema induced by influenza virus (Hong et al, 2015), and potassium canrenoate, the main metabolite of spironolactone in vivo, is an anti-aldosteronic/diuretic used in the treatment of hypertensive patients.…”

Section: Discussionmentioning

confidence: 99%

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

et al. 2020

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The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors.

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Section: Discussionmentioning

confidence: 99%

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

et al. 2020

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“…Of interest, some of these agents have been reported for the potential use as anti-HIV agents (Řezanka et al, 2009), while oleanolic acid that might function as a broad spectrum entry inhibitor of influenza viruses (Yang et al, 2018). On the other side, betulinic acid has been demonstrated useful in reducing inflammation and pulmonary edema induced by influenza virus (Hong et al, 2015), and potassium canrenoate, the main metabolite of spironolactone in vivo, is an anti-aldosteronic/diuretic used in the treatment of hypertension patients.…”

Section: Discussionmentioning

confidence: 99%

Hijacking SARS-Cov-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on receptor binding region

Carino

Moraca

Fiorillo

et al. 2020

Preprint

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The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In the light of the urgent need to identify novel approaches to be used in the emergency phase, a largely explored strategy has been the repurpose of clinically available drugs as new antivirals, by targeting different viral proteins. In this paper, we describe a drug repurposing strategy based on a virtual screening of druggable pockets located in the central -sheet core of the SARS-CoV-2 Spike protein RBD supported by in vitro tests identifying several steroidal derivatives as SARS-CoV-2 entry inhibitors. Our results demonstrate that several potential binding sites exist in the SARS CoV-2 S protein, and that the occupancy of these pockets reduces the ability of the S protein RBD to bind to the ACE2 consensus in vitro. In particular, natural occurring and clinically available steroids as glycyrrhetinic and oleanolic acids, as well as the bile acids derivatives glyco-UDCA and obeticholic acid have been shown to be effective in preventing virus entry in the case of low viral load. All together, these results might help to define novel approaches to reduce the viral load by using SARS-CoV-2 entry inhibitors.

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“…The amino acid sequence of influenza matrix protein 2 ectodomain (M2e) is highly conserved among human seasonal influenza A viruses (Deng et al 2018a). Multivalent oleanolic acid protein conjugates as nonglycosylated neomucin mimics for the capture and entry inhibition of influenza A viruses (H1N1, H3N2, and H9N2) designed by Yang et al (2018) were found to be comparable to natural glycosylated mucin, suggesting that this material could potentially be used as anti-infective barriers to prevent virus from invading host cells. Bernasconi et al (2018) developed a fusion protein with three copies of the ectodomain of matrix protein 2, which is one of the most explored conserved influenza A virus antigens for a broadly protective vaccine and incorporated it into porous maltodextrin NPs to enhance its protective ability and the formulation resulted in broadly protective immunity against a lethal infection with heterosubtypic influenza virus, immune protection being mediated by enhanced levels of lung-resident CD4 + T cells as well as anti-HA and anti-M2e serum IgG and local IgA antibodies.…”

Section: Influenza a Viruses Subtypes H3n2 And H1n1mentioning

confidence: 99%

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

Jampílek

Kráľová

2019

Nanotheranostics

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Various viruses can be considered as one of the most frequent causes of human diseases, from mild illnesses to really serious sicknesses that end fatally. Numerous viruses are also pathogenic to animals and plants, and many of them, mutating, become pathogenic also to humans. Several cases of affecting humans by originally animal viruses have been confirmed. Viral infections cause significant morbidity and mortality in humans, the increase of which is caused by general immunosuppression of the world population, changes in climate, and overall globalization. In spite of the fact that the pharmaceutical industry pays great attention to human viral infections, many of clinically used antivirals demonstrate also increased toxicity against human cells, limited bioavailability, and thus, not entirely suitable therapeutic profile. In addition, due to resistance, a combination of antivirals is needed for life-threatening infections. Thus, the development of new antiviral agents is of great importance for the control of virus spread. On the other hand, the discovery and development of structurally new antivirals represent risks. Therefore, another strategy is being developed, namely the reformulation of existing antivirals into nanoformulations and investigation of various metal and metalloid nanoparticles with respect to their diagnostic, prophylactic, and therapeutic antiviral applications. This chapter is focused on nanoscale materials/formulations with the potential to be used for the treatment or inhibition of the spread of viral diseases caused by human immunodeficiency virus, influenza A viruses (subtypes H3N2 and H1N1), avian influenza and swine influenza viruses, respiratory syncytial virus, herpes simplex virus, hepatitis B and C viruses, Ebola and Marburg viruses, Newcastle disease virus, dengue and Zika viruses, and pseudorabies virus. Effective antiviral long-lasting and target-selective nanoformulations developed for oral, intravenous, intramuscular, intranasal, intrarectal, intravaginal, and intradermal applications are discussed.

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Multivalent oleanolic acid human serum albumin conjugate as nonglycosylated neomucin for influenza virus capture and entry inhibition

Cited by 29 publications

References 43 publications

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

Hijacking SARS-Cov-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on receptor binding region

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

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