Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus.Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).Ginkgolic acids are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. Ginkgo biloba extracts (GBE) have been used as herbal supplements since at least the 16 th century and remain widely in use 1 . Major constituents of GBE include terpine trilactones (ginkgolide A, B, C, J, and bilobalide), flavonoid glycosides (quercetin and rutin), as well as Ginkgolic acids 2 . Ginkgolic acids are a mixture of several 2-hydroxy-6-alkylbenzoic acids in which the most common alkyl chains contain 13, 15, or 17 carbons. The 15 and 17 carbon chains are unsaturated at positions 8 and 10, respectively. The 3 Ginkgolic acid (GA) structures are, therefore, designated C13:0, C15:1, and C17:1 (Table S1) 3 .GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; potential rescue of amyloid-β (Aβ) induced synaptic impairment; and inhibition of HIV protease activity as well as HIV viral replication 4-7 . GA was also reported to have activity against Escherichia coli and Staphylococcus aureus 8 . Several ways in which GA works have been suggested including by SUMOylation inhibition activity; blocking formation of the E1-SUMO intermediate 9 ;...

Herpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs against HSV infection are nucleoside analogues including acyclovir (ACV), famciclovir, and valacyclovir. Although these nucleoside analogues reduce morbidity and mortality in immunocompetent individuals, ACV-resistant HSV strains (ACVR-HSV) have been isolated from immunocompromised patients. Thus, ACVR-HSV infection poses a critical emerging public health concern. Recently, we reported that ginkgolic acid (GA) inhibits HSV-1 by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we showed GA affords a broad spectrum of fusion inhibition of all three classes of fusion proteins, including those of HIV, Ebola, influenza A and Epstein Barr viruses. Here we report GA’s antiviral activity against HSV-1 skin infection in BALB/cJ mice. GA-treated mice demonstrated a significantly reduced mortality rate and decreased infection scores compared to controls treated with dimethylsulfoxide (DMSO)-vehicle. Furthermore, GA efficiently inhibited ACVR-HSV-1 strain 17+ in vitro and in vivo. Since GA’s mechanism of action includes virucidal activity and fusion inhibition, it is expected to work alone or synergistically with other anti-viral drugs, and we anticipate it to be effective against additional cutaneous and potentially systemic viral infections.

Epstein–Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90–95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to various epithelial malignancies such as nasopharyngeal and gastric cancer. Recent evidence suggests a link between EBV and breast cancer. Additionally, there are other, rarer cancers with weaker evidence linking them to EBV. In this review, we discuss the currently known epithelial malignancies associated with EBV. Additionally, we discuss and establish which treatments and therapies are most recommended for each cancer associated with EBV.

While a rising prevalence of anemia in the United States was reported in older studies, recent data are lacking. To estimate the prevalence and time trends of anemia in the United States and to examine how these estimates differ by gender, age, race, and household income to poverty threshold ratio (HIPR), we used the National Health and Nutrition Examination Surveys from 1999 to 2020. The presence of anemia was determined using the World Health Organization criteria. Survey-weighted raw and adjusted prevalence ratios (PRs) were determined using generalized linear models for the overall population and by gender, age, race, and HIPR. In addition, an interaction between gender and race was explored. Complete data on anemia, age, gender, and race were available on 87,554 participants (mean age = 34.6 years, women = 49.8%, Whites = 37.3%). Anemia prevalence increased from 4.03% during the 1999–2000 survey cycle to 6.49% during 2017–2020. In adjusted analyses, anemia prevalence was higher in >65 than in 26–45 years old (PR = 2.14, 95% confidence interval (CI) = 1.95, 2.35), in Blacks than Whites (PR = 3.97, 95% CI = 3.63, 4.35), in women than men (PR = 1.98, 95% CI = 1.83, 2.13), and in those with HIPR ≤ 1 than >4 (PR = 0.68, 95% CI = 0.61, 0.75). Gender modified the relationship between anemia and race; when compared to their male counterparts, Black, Hispanic, and other women had higher anemia prevalence than White women (all interaction p values <0.05). The anemia prevalence in the United States has risen from 1999 to 2020 and remains high among the elderly, minorities, and women. The difference in anemia prevalence between men and women is larger in non-Whites.

Type 1 diabetes (T1D) is an autoimmune disease resulting in pancreatic β-cell destruction. Coxsackievirus B3 (CVB3) infection and melanoma differentiation-associated protein 5 (MDA5)-dependent antiviral responses are linked with T1D development. Mutations within IFIH1, encoding for MDA5, are correlated with T1D susceptibility, but how these mutations contribute to T1D remains unclear. Utilizing non-obese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (ΔHel1), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses. Spontaneous T1D developed in female NOD and KO mice similarly, but was significantly delayed in ΔHel1 mice that may be partly due to a concomitant increase in myeloidderived suppressor cells. Interestingly, KO male mice had increased spontaneous T1D compared to NOD mice. While NOD and KO mice developed CVB3-accelerated T1D, ΔHel1 mice were protected partly due to decreased type I interferons, pancreatic-infiltrating TNF + macrophages, IFNγ + CD4 + T cells, and perforin + CD8 + T cells. Furthermore, ΔHel1 MDA5 protein had reduced ATP hydrolysis compared to wild-type MDA5. Our results suggest that dampened MDA5 function delays T1D, yet loss of MDA5 promotes T1D.