Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Recombinant Rod Domain of Vimentin Reduces SARS-CoV-2 Viral Replication by Blocking Spike Protein–ACE2 Interactions

Although the SARS-CoV-2 vaccination is the primary preventive intervention, there are still few antiviral therapies available, with current drugs decreasing viral replication once the virus is intracellular. Adding novel drugs to target additional points in the viral life cycle is paramount in preventing future pandemics. The purpose of this study was to create and test a novel protein to decrease SARS-CoV-2 replication. We created the recombinant rod domain of vimentin (rhRod) in E. coli and used biolayer interferometry to measure its affinity to the SARS-CoV-2 S1S2 spike protein and the ability to block the SARS-CoV-2–ACE2 interaction. We performed plaque assays to measure rhRod’s effect on SARS-CoV-2 replication in Vero E6 cells. Finally, we measured lung inflammation in SARS-CoV-2-exposed K18-hACE transgenic mice given intranasal and intraperitoneal rhRod. We found that rhRod has a high affinity for the S1S2 protein with a strong ability to block S1S2–ACE2 interactions. The daily addition of rhRod decreased viral replication in Vero E6 cells starting at 48 h at concentrations >1 µM. Finally, SARS-CoV-2-infected mice receiving rhRod had decreased lung inflammation compared to mock-treated animals. Based on our data, rhRod decreases SARS-CoV-2 replication in vitro and lung inflammation in vivo. Future studies will need to evaluate the protective effects of rhRod against additional viral variants and identify the optimal dosing scheme that both prevents viral replication and host lung injury

The vimentin rod domain blocks P-selectin-P-selectin glycoprotein ligand 1 interactions to attenuate leukocyte adhesion to inflamed endothelium.

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling suggesting that rhRod binds P-selectin at or near the PSGL-1 binding site. Using bio-layer interferometry, rhRod decreases PSGL-1 binding to immobilized P-selectin, corroborating the in silico data. Under parallel-plate flow, rhRod blocks leukocyte adhesion to fibrin(ogen)-captured platelets, P-selectin/Fc-coated channels, and IL-1β/IL-4-co-stimulated human umbilical vein endothelial cells. Finally, using intravital microscopy in endotoxemic C57Bl/6 mice, rhRod co-localizes with P-selectin in the hepatic sinusoids and decreases neutrophil adhesion to hepatic sinusoids. These data suggest a potential role for rhRod in attenuating inflammation through directly blocking P-selectin-PSGL-1 interactions