Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, a disease of humans and animals. It is primarily transmitted through direct contact with contaminated soil and surface water. The epidemiology of this pathogen in Africa, including Uganda, is largely unknown. The objectives of this study were to estimate the seroprevalence of B. pseudomallei in pigs slaughtered in central Uganda and to identify potential hotspots for this pathogen in the country. A total of 1035 pig sera were analyzed for serological responses to B. pseudomallei with type A and type B LPS using OPS type A and OPS type B ELISAs. Of the 1035 samples, 75 (7.25%, 95% CI: 5.8–9%) were seropositive to the OPS-A ELISA using a two standard deviations (SD) cutoff and 19 (1.84%, 95% CI: 1.2–2.9%) at 3 SD. For the OPS-B ELISA, 93/1035 (8.99%, 95% CI: 7.4–10.9%) were seropositive at the 2 SD cutoff, and 28/1035 (2.71%, 95% CI: 1.9–3.9%) at the 3 SD cutoff. Pigs slaughtered in central Uganda were exposed to B. pseudomallei, and there is a higher seroprevalence in the rainy months. Public health awareness campaigns about melioidosis may be needed.

(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.

(1) Background: Burkholderia pseudomallei is an environmentally mediated saprophytic pathogen that can cause severe disease in humans. It is well known that B. pseudomallei survives in tropical moist soil environments worldwide, but melioidosis is gaining recognition as a public and veterinary health issue in Vietnam. The contribution of animals to human disease is unknown, necessitating further investigation. (2) Methods: Swine sera were collected from two populations, one grazing and one commercially farmed, from three provinces in Vietnam. ELISAs utilizing B. pseudomallei capsular polysaccharide (CPS), outer polysaccharide (OPS), and Hcp1 protein were used to screen serum samples. Positive samples were mapped to the commune level. Seroprevalence calculations and pig population estimates were used to approximate number of swine exposures per commune. (3) Results: Grazing pigs from Hoa Binh had significantly higher seropositivity levels (11.4%, 95% CI: 9.7–13.1) compared to farmed pigs from Ha Tinh and Nghe An (4%, 95% CI: 3.3–4.7). Average swine seropositivity rates were ~6.3% (95% CI: 5–7.9), higher than previously identified in Vietnam (~0.88%). (4) Conclusions: Initial serological sampling identified a significant number of seropositive and potential melioidosis infections occurring in swine in Vietnam. This work is a critical step in understanding the role swine may play in the epidemiology of human melioidosis in Vietnam.

The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy. This underscores the urgent need to investigate alternative therapeutic approaches. Sigma receptors have been unexpectedly linked to the SARS-CoV-2 life cycle due to the direct antiviral effect of their ligands. Coronavirus-induced cell stress facilitates the formation of an ER-derived complex conducive to its replication. Sigma receptor ligands are believed to prevent the formation of this complex. Repurposing FDA-approved drugs for COVID-19 offers a timely and cost-efficient strategy to find treatments with established safety profiles. Notably, diphenhydramine, a sigma receptor ligand, is thought to counteract the virus by inhibiting the creation of ER-derived replication vesicles. Furthermore, lactoferrin, a well-characterized immunomodulatory protein, has shown antiviral efficacy against SARS-CoV-2 both in laboratory settings and in living organisms. In the present study, we aimed to explore the impact of sigma receptor ligands on SARS-CoV-2-induced mortality in ACE2-transgenic mice. We assessed the effects of an investigational antiviral drug combination comprising a sigma receptor ligand and an immunomodulatory protein. Mice treated with sigma-2 receptor ligands or diphenhydramine and lactoferrin exhibited improved survival rates and rapid rebound in mass following the SARS-CoV-2 challenge compared to mock-treated animals. Clinical translation of these findings may support the discovery of new treatment and research strategies for SARS-CoV-2.