Antiviral Activity and Mechanism of Action of Endoplasmic Reticulum Glucosidase Inhibitors: A Mini Review

Hemocyanins are large and versatile glycoproteins performing various immunological and biological functions in many marine invertebrates including arthropods and molluscs. This review discusses the various pharmacological applications of mollusc hemocyanin such as antiviral activity, immunostimulatory and anticancer properties that have been reported in the literature between the years 2000 and 2016. Emphasis is placed on a better mechanistic understanding of hemocyanin as a therapeutic agent. Elucidation of the mechanism of action is essential to improve the clinical efficacy and for a better understanding of some endogenous immunological functions of this complex glycoprotein.

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Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus

Life ◽

10.3390/life11010016 ◽

2020 ◽

Vol 11 (1) ◽

pp. 16

Author(s):

Andreza C. Santana ◽

Ronaldo C. Silva Filho ◽

José C. J. M. D. S. Menezes ◽

Diego Allonso ◽

Vinícius R. Campos

Keyword(s):

Antiviral Activity ◽

Mechanism Of Action ◽

Heterocyclic Compounds ◽

Chikungunya Virus ◽

Antiviral Agents ◽

Antiviral Drug ◽

Important Class ◽

Available Nitrogen ◽

Global Threat ◽

Present Understanding

Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya fever, characterized by a severe arthralgia (joint pains) that can persist for several months or years in some individuals. Until now, no vaccine or specific antiviral drug is commercially available. Nitrogen heterocyclic scaffolds are found in medications, such as aristeromycin, favipiravir, fluorouracil, 6-azauridine, thioguanine, pyrimethamine, among others. New families of natural and synthetic nitrogen analogous compounds are reported to have significant anti-CHIKV effects. In the present work, we focus on these nitrogen-based heterocyclic compounds as an important class with CHIKV antiviral activity. We summarize the present understanding on this class of compounds against CHIKV and also present their possible mechanism of action.

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Towards Inhibition of Vif-APOBEC3G Interaction: Which Protein to Target?

Advances in Virology ◽

10.1155/2010/649315 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Iris Cadima-Couto ◽

Joao Goncalves

Keyword(s):

Antiviral Activity ◽

Protein Binding ◽

Mechanism Of Action ◽

Cellular Immunity ◽

Viral Infectivity ◽

Binding Partners ◽

Viral Infectivity Factor ◽

Vif Protein ◽

Hiv 1 ◽

Antiretroviral Activity

APOBEC proteins appeared in the cellular battle against HIV-1 as part of intrinsic cellular immunity. The antiretroviral activity of some of these proteins is overtaken by the action of HIV-1 Viral Infectivity Factor (Vif) protein. Since the discovery of APOBEC3G (A3G) as an antiviral factor, many advances have been made to understand its mechanism of action in the cell and how Vif acts in order to counteract its activity. The mainstream concept is that Vif overcomes the innate antiviral activity of A3G by direct protein binding and promoting its degradation via the cellular ubiquitin/proteasomal pathway. Vif may also inhibit A3G through mechanisms independent of proteasomal degradation. Binding of Vif to A3G is essential for its degradation since disruption of this interaction is predicted to stimulate intracellular antiviral immunity. In this paper we will discuss the different binding partners between both proteins as one of the major challenges for the development of new antiviral drugs.

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Brilacidin, a COVID-19 Drug Candidate, demonstrates broad-spectrum antiviral activity against human coronaviruses OC43, 229E and NL63 through targeting both the virus and the host cell

10.1101/2021.11.04.467344 ◽

2021 ◽

Author(s):

Yanmei Hu ◽

Hyunil Jo ◽

William DeGrado ◽

Jun Wang

Keyword(s):

Antiviral Activity ◽

Cell Surface ◽

Host Cell ◽

Mechanism Of Action ◽

Broad Spectrum ◽

Drug Candidate ◽

Host Defense Peptides ◽

Antibiotic Drug ◽

Host Cell Surface ◽

Human Coronaviruses

Brilacidin, a mimetic of host defense peptides (HDPs), is currently in phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against SARS-CoV-2 by inactivating the virus. In this work, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, a HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.

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A Review on the Use of Antimicrobial Peptides to Combat Porcine Viruses

Antibiotics ◽

10.3390/antibiotics9110801 ◽

2020 ◽

Vol 9 (11) ◽

pp. 801

Author(s):

Guihong Pen ◽

Na Yang ◽

Da Teng ◽

Ruoyu Mao ◽

Ya Hao ◽

...

Keyword(s):

Antiviral Activity ◽

Infectious Diseases ◽

Antimicrobial Peptides ◽

Mechanism Of Action ◽

Animal Husbandry ◽

New Drugs ◽

Swine Production ◽

Therapeutic Measures ◽

Future Potential ◽

Research Situation

Viral infectious diseases pose a serious threat to animal husbandry, especially in the pig industry. With the rapid, continuous variation of viruses, a series of therapeutic measures, including vaccines, have quickly lost their efficacy, leading to great losses for animal husbandry. Therefore, it is urgent to find new drugs with more stable and effective antiviral activity. Recently, it has been reported that antimicrobial peptides (AMPs) have great potential for development and application in animal husbandry because of their significant antibacterial and antiviral activity, and the antiviral ability of AMPs has become a research hotspot. This article aims to review the research situation of AMPs used to combat viruses in swine production of animal husbandry, clarify the mechanism of action of AMPs on viruses and raise some questions, and explore the future potential of AMPs in animal husbandry.

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