Antivirals targeting paramyxovirus membrane fusion

Contreras, Erik; Monreal, I. Abrrey; Ruvalcaba, Martin; Ortega, Victoria; Aguilar, Hector C.

doi:10.1016/j.coviro.2021.09.003

Cited by 7 publications

(5 citation statements)

References 198 publications

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“…Since C proteindeficient viruses are highly attenuated, they could serve as novel live-attenuated vaccines. In addition, novel antiviral therapeutics may target some C protein functions, to be used in combination with existing fusion and polymerase inhibitors [203][204][205]. In consideration of the multiple functions of paramyxovirus C proteins in the control of virus replication and of the host innate immune response, we propose that C should stand for "control".…”

Section: Discussionmentioning

confidence: 99%

C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response

Siering

Cattaneo

Pfaller

2022

Viruses

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Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed “C”, are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the phosphoprotein gene. Some viruses express nested sets of C proteins that exert their functions in different locations: In the nucleus, they interfere with cellular transcription factors that elicit innate immune responses; in the cytoplasm, they associate with viral ribonucleocapsids and control polymerase processivity and orderly replication, thereby minimizing the activation of innate immunity. In addition, certain C proteins can directly bind to, and interfere with the function of, several cytoplasmic proteins required for interferon induction, interferon signaling and inflammation. Some C proteins are also required for efficient virus particle assembly and budding. C-deficient viruses can be grown in certain transformed cell lines but are not pathogenic in natural hosts. C proteins affect the same host functions as other phosphoprotein gene-encoded proteins named V but use different strategies for this purpose. Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments.

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Section: Discussionmentioning

confidence: 99%

C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response

Siering

Cattaneo

Pfaller

2022

Viruses

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“…Activation of those containing both a CXXC and a CX6CC motif appears to involve disulfide exchange following receptor binding ( 4 ). Binding to cell surface receptors also triggers the fusion proteins of paramyxoviruses ( 34 ), but for these, binding is via a separate viral glycoprotein, alternatively termed H, G, or HN. Upon engagement, the binding protein undergoes a change that is relayed to, and thereby triggers, F ( 35 , 36 ).…”

Section: Sites Of Enveloped Virus Fusionmentioning

confidence: 99%

Viral Membrane Fusion: A Dance Between Proteins and Lipids

White,

Ward,

Odongo

et al. 2023

Annual Review of Virology

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There are at least 21 families of enveloped viruses that infect mammals, and many contain members of high concern for global human health. All enveloped viruses have a dedicated fusion protein or fusion complex that enacts the critical genome-releasing membrane fusion event that is essential before viral replication within the host cell interior can begin. Because all enveloped viruses enter cells by fusion, it behooves us to know how viral fusion proteins function. Viral fusion proteins are also major targets of neutralizing antibodies, and hence they serve as key vaccine immunogens. Here we review current concepts about viral membrane fusion proteins focusing on how they are triggered, structural intermediates between pre- and postfusion forms, and their interplay with the lipid bilayers they engage. We also discuss cellular and therapeutic interventions that thwart virus-cell membrane fusion.

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“…CBGA and CBDA were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351 [ 12 ]. Small-molecule inhibitors of viral fusion have been effective against the human immunodeficiency virus, influenza, and paramyxovirus [ 13 , 14 , 15 , 16 ]. Cannabinoids may similarly have the potential to prevent infection by SARS-CoV-2.…”

Section: Cannabinoids For Early Sars-cov-2 Infectionmentioning

confidence: 99%

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review

Scott,

Hall,

Zhou

et al. 2023

JCM

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Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.

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Antivirals targeting paramyxovirus membrane fusion

Cited by 7 publications

References 198 publications

C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response

C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response

Viral Membrane Fusion: A Dance Between Proteins and Lipids

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review

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