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Viruses rely on host cells for energy and synthesis machinery required for genome replication and particle assembly. Due to the dependence of viruses on host cells, viruses have evolved multiple mechanisms by which they can induce metabolic changes in the host cell to suit their specific requirements. The host immune response also involves metabolic changes to be able to react to viral insult. Polyamines are small ubiquitously expressed polycations, and their metabolism is critical for viral replication and an adequate host immune response. This is due to the variety of functions that polyamines have, ranging from condensing DNA to enhancing the translation of polyproline-containing proteins through the hypusination of eIF5A. Here, we review the diverse mechanisms by which viruses exploit polyamines, as well as the mechanisms by which immune cells utilize polyamines for their functions. Furthermore, we highlight potential avenues for further study of the host-virus interface. [ABSTRACT FROM AUTHOR]

Background Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection. Methods We isolated single peripheral blood plasmablasts from children with KD 1–3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen. Results Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P  < .01), recognized the KD peptide antigen. Conclusions These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem. [ABSTRACT FROM AUTHOR]

Understanding the magnitude of responses to vaccination during the ongoing SARS-CoV-2 pandemic is essential for ultimate mitigation of the disease. Here, we describe a cohort of 102 subjects (70 COVID-19-naïve, 32 COVID-19-experienced) who received two doses of one of the mRNA vaccines (BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna)). We document that a single exposure to antigen via infection or vaccination induces a variable antibody response which is affected by age, gender, race, and co-morbidities. In response to a second antigen dose, both COVID-19-naïve and experienced subjects exhibited elevated levels of anti-spike and SARS-CoV-2 neutralizing activity; however, COVID-19-experienced individuals achieved higher antibody levels and neutralization activity as a group. The COVID-19-experienced subjects exhibited no significant increase in antibody or neutralization titer in response to the second vaccine dose (i.e., third antigen exposure). Finally, we found that COVID-19-naïve individuals who received the Moderna vaccine exhibited a more robust boost response to the second vaccine dose (p = 0.004) as compared to the response to Pfizer–BioNTech. Ongoing studies with this cohort will continue to contribute to our understanding of the range and durability of responses to SARS-CoV-2 mRNA vaccines. [ABSTRACT FROM AUTHOR]

Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics. One way to facilitate development is to repurpose molecules already used clinically. By screening such compounds, we can accelerate antiviral development. Here, we screened compounds from the National Institutes of Health's Developmental Therapeutic Program for activity against chikungunya virus, an alphavirus that is responsible for a significant outbreak in the Americas in 2013. Using this library, we identified several compounds with known antiviral activity, as well as several novel antivirals. Given its favorable in vitro activity and well-described in vivo activity, as well as its broad availability, we focused on bisacodyl, a laxative used for the treatment of constipation, for follow-up studies. We find that bisacodyl inhibits chikungunya virus infection in a variety of cell types, over a range of concentrations, and over several rounds of replication. We find that bisacodyl does not disrupt chikungunya virus particles or interfere with their ability to attach to cells, but, instead, bisacodyl inhibits virus replication. Finally, we find that bisacodyl is broadly antiviral against a variety of RNA viruses, including enteroviruses, flaviviruses, bunyaviruses, and alphaviruses; however, it exhibited no activity against the DNA virus vaccinia virus. Together, these data highlight the power of compound screening to identify novel antivirals and suggest that bisacodyl may hold promise as a broad-spectrum antiviral.