Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells

Su, Xiaojie; Wang, Qian; Wen, Yumei; Jiang, Shibo; Lu, Lu

doi:10.3389/fmicb.2020.01063

Cited by 28 publications

(21 citation statements)

References 159 publications

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“…In this manuscript, we demonstrate brilacidin exhibits robust inhibition of SARS-CoV-2 in Vero cells and Calu-3 cells, and in two strains of the virus. Likely to function as a viral entry inhibitor [ 73 , 74 , 75 ], the proposed mechanism of action for brilacidin includes affecting the integrity of the viral membrane and interfering with viral entry. Brilacidin also exhibited an excellent synergistic inhibitory profile against SARS-CoV-2 in combination with remdesivir.…”

Section: Discussionmentioning

confidence: 99%

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture

Bakovic

Risner

Bhalla

et al. 2021

Viruses

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin—a de novo designed synthetic small molecule that captures the biological properties of HDPs—on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.

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Section: Discussionmentioning

confidence: 99%

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture

Bakovic

Risner

Bhalla

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…In this manuscript, we demonstrate brilacidin exhibits robust inhibition of SARS-CoV-2 in Vero cells and Calu-3 cells, supporting brilacidin as a promising novel drug candidate for the treatment of COVID-19. Functioning as a viral entry inhibitor, 95, 96, 97 proposed mechanisms of action for brilacidin include affecting the integrity of the viral membrane and preventing viral binding to cells. More detailed mechanistic studies are planned.…”

Section: Discussionmentioning

confidence: 99%

Brilacidin, a COVID-19 Drug Candidate, Exhibits PotentIn VitroAntiviral Activity Against SARS-CoV-2

Bakovic

Risner

Bhalla

et al. 2020

Preprint

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than one million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin−a de novo designed synthetic small molecule that captures the biological properties of HDPs−on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is primarily a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin has demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 and thus supports brilacidin as a promising COVID-19 drug candidate. Highlights: Brilacidin potently inhibits SARS-CoV-2 in an ACE2 positive human lung cell line. Brilacidin achieved a high Selectivity Index of 426 (CC50=241µM/IC50=0.565µM). Brilacidin's main mechanism appears to disrupt viral integrity and impact viral entry. Brilacidin and remdesivir exhibit excellent synergistic activity against SARS-CoV-2. Significance Statement: SARS-CoV-2, the emergent novel coronavirus, has led to the current global COVID-19 pandemic, characterized by extreme contagiousness and high mortality rates. There is an urgent need for effective therapeutic strategies to safely and effectively treat SARS-CoV-2 infection. We demonstrate that brilacidin, a synthetic small molecule with peptide-like properties, is capable of exerting potent in vitro antiviral activity against SARS-CoV-2, both as a standalone treatment and in combination with remdesivir, which is currently the only FDA-approved drug for the treatment of COVID-19.

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“…Entry inhibitors provide a significant advantage compared to other inhibitor-classes because they block infection before the virus infects the cell. Obviously, this is a feature that reverse-transcriptase, protease, and integrase inhibitors do not possess [ 221 ].…”

Section: Treatment Of Hiv-1 Infection With Entry Inhibitorsmentioning

confidence: 99%

HIV-1 Entry and Prospects for Protecting against Infection

et al. 2021

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Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered. Given that HIV-1 is most often transmitted mucosally, strategies designed to protect against infection need to be effective at mucosal portals of entry. These strategies need to contend also with cell-free and cell-associated transmitted/founder (T/F) virus forms; both can initiate and establish infection. This review will discuss how insight from the current model of HIV-1 mucosal transmission and cell entry has highlighted challenges in developing effective strategies to prevent infection. First, we examine key viral and host factors that play a role in transmission and infection. We then discuss preventive strategies based on antibody-mediated protection, with emphasis on targeting T/F viruses and mucosal immunity. Lastly, we review treatment strategies targeting viral entry, with focus on the most clinically advanced entry inhibitors.

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Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells

Cited by 28 publications

References 159 publications

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture

Brilacidin, a COVID-19 Drug Candidate, Exhibits PotentIn VitroAntiviral Activity Against SARS-CoV-2

HIV-1 Entry and Prospects for Protecting against Infection

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