Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

Current literature values of 2,4,6-trinitrotoluene (TNT) solubility in water vary widely from 100 to 200 mg/L at room temperature. We investigated the effects of temperature and pH on the solubility of both reference TNT and field neat TNT obtained from the Alabama Army Ammunition Plant (AAAP), Childersburg, AL. The TNT solubility determined from this study was significantly lower than that of Taylor and Rinkenbach, which was cited by several reference chemical handbooks and articles. However, the values reported by the Merck Index and the Lange's Handbook of Chemistry compared well with our values. TNT solubility dropped rapidly as the pH increased. Three unknown HPLC peaks were observed at high pH, indicating a possibility of forming unknown transformation products. Both reference and field neat TNT solubility agreed well. A semiempirical solubility correlation was developed to predict the solubility of TNT at a temperature range from 6 °C to 42 °C.

SignificanceInhibitors of dengue virus, a mosquito-borne pathogen, are urgently needed. Virally encoded NS2B/3, a two-subunit serine proteinase, is responsible for many cleavages within the viral polyprotein. We demonstrate that two cleavage sites flanking NS3 and one that is internal are self-processing. This strict intramolecular cleavage dictates that, if uncleaved precursors can inhibit viral growth, this phenotype will be trans-dominant. Indeed, a mutation that abrogates one of the self-processing sites caused trans-dominant inhibition of wild-type virus. This site is also the most susceptible to a dengue proteinase inhibitor, providing a compelling rationale for its efficacy. We suggest that explicit targeting of specific intramolecular cleavage sites will be an effective antiviral strategy that can suppress multiple variants in an intracellular quasispecies.

Patients with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection give rise to SARS-CoV-2 environmental contamination during childbirth.