Publications by authors named "Callahan V"

Article Synopsis
  • - Alphaviruses pose a threat to public health, and two monoclonal antibodies (mAbs), SKT05 and SKT20, show promise in providing protection against Venezuelan equine encephalitis virus (VEEV) in mouse models.
  • - SKT20's effectiveness relies on Fc effector functions to prevent death from VEEV, while SKT05 can control viral spread and replication without these functions initially, but requires them later for full efficacy.
  • - The study highlights how antibody avidity (strength of binding) is crucial for mAb effectiveness and suggests that understanding Fc-dependent mechanisms can help in developing better therapeutic treatments for alphavirus infections.
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We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S.

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Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups.

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The innate immune protection provided by cationic antimicrobial peptides (CAMPs) has been shown to extend to antiviral activity, with putative mechanisms of action including direct interaction with host cells or pathogen membranes. The lack of therapeutics available for the treatment of viruses such as Venezuelan equine encephalitis virus (VEEV) underscores the urgency of novel strategies for antiviral discovery. American alligator plasma has been shown to exhibit strong in vitro antibacterial activity, and functionalized hydrogel particles have been successfully employed for the identification of specific CAMPs from alligator plasma.

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Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System.

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Article Synopsis
  • SARS-CoV-2 is the virus responsible for COVID-19, leading to severe cases that can cause serious lung damage, often requiring mechanical ventilation due to conditions like acute lung injury and ARDS.
  • The study highlighted that infection with SARS-CoV-2 results in an inflammatory response marked by elevated levels of specific chemokines (CXCL9, CXCL10, CXCL11) and cytokines (IL-6, TNFα, IFN-γ) in lung cells and infected mouse models.
  • It found that blocking certain signaling pathways, particularly the AKT pathway, significantly reduces the expression of these harmful chemokines, suggesting potential therapeutic targets to mitigate inflammation and improve outcomes in COVID-19 patients.
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Background: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry.

Methods: We developed a cell-based assay to identify TMPRSS2 inhibitors.

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Alphaviruses are a genus of the family and are widely distributed across the globe. Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), cause encephalitis and neurological sequelae while chikungunya virus (CHIKV) and Sindbis virus (SINV) cause arthralgia. There are currently no approved therapeutics or vaccines available for alphaviruses.

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Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from contrived transport medium and saliva samples using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus from 1 mL samples prior to RNA extraction, substantially improving detection of virus using real-time RT-PCR across a range of viral titers (100-1,000,000 viral copies/mL) and enabling detection of virus using the 2019 nCoV CDC EUA Kit down to 100 viral copies/mL. This method is compatible with commercially available nucleic acid extraction kits (i.

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Article Synopsis
  • * Researchers discovered that alpha 1 antitrypsin (A1AT), a human protease inhibitor, can inhibit TMPRSS2, providing a new approach to target SARS-CoV-2 entry into host cells.
  • * The findings suggest that enhancing A1AT levels or using A1AT as a treatment could help reduce the severity of COVID-19 by preventing the virus from efficiently entering host cells.
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Nanotrap® (NT) particles are hydrogel microspheres developed for target analyte separation and discovery applications. NT particles consist of cross-linked N-isopropylacrylamide (NIPAm) copolymers that are functionalized with a variety of chemical affinity baits to enable broad-spectrum collection and retention of target proteins, nucleic acids, and pathogens. NT particles have been previously shown to capture and enrich arboviruses including Rift Valley fever and Venezuelan equine encephalitis viruses.

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Zika virus (ZIKV) is a re-emerging Flavivirus that has been linked to microcephaly and other neurological pathologies. In this study, phloretin, a glucose transporter inhibitor naturally derived from plants, was used to investigate the glucose dependence of ZIKV replication in host cells. The results showed that phloretin significantly decreased infectious titres of two ZIKV strains, namely MR766 (African genotype) and PRVABC59 (Puerto Rico genotype).

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Article Synopsis
  • New World alphaviruses, including Venezuelan, eastern, and western equine encephalitis viruses, pose significant health risks due to their potential to cause severe illness and death in humans, and there are concerns about their use as bioweapons.
  • *Currently, there are no FDA-approved antiviral treatments specifically for these viruses, highlighting the urgent need for research in this area.
  • *This review focuses on the functions of various viral proteins and discusses possible therapeutic targets, noting an increasing interest in non-structural protein 3, capsid, and E2 proteins, while emphasizing the need for further investigation into host protein interactions with other viral proteins.
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Objective/background: The quality of life (QOL) of hematopoietic stem cell transplant (HSCT) patients and their caregivers decreases during the first 8 days after HSCT.

Methods: This prospective pilot study collected preliminary data on the impact of posttransplant living arrangements (hospital hospitality house [HHH] vs. hotel, apartment, or house ["hotel"]) and other factors on the QOL of HSCT patients and their caregivers.

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