ABSTRACT
We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies.
Subject(s)
COVID-19 , Single-Domain Antibodies , Antibodies, Viral , Humans , Membrane Glycoproteins/metabolism , Neutralization Tests , SARS-CoV-2/genetics , Single-Domain Antibodies/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolismABSTRACT
IgG4-related disease (IgG4-RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4-RD of the paratestis. A 74-year-old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4-RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case.
Subject(s)
Autoimmune Diseases/pathology , Immunoglobulin G4-Related Disease/pathology , Immunoglobulin G/immunology , Plasma Cells/pathology , Aged , Autoimmune Diseases/diagnosis , Autoimmune Diseases/immunology , Biopsy/methods , Humans , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/immunology , Immunohistochemistry/methods , Male , Salivary Glands/pathologyABSTRACT
Anti-Leishmania in vitro and in vivo activities of various rhodacyanine derivatives have been examined. Among them, the fluorinatied variant SJL-01 (8) showed IC(50) of 0.011 microM against Leishmania donovani strain MHOM/ET/67/L82 (selective index of >15000) and 95-97% inhibition against L. donovani strain MHOM/ET/67/HU in female BALB/c mice by 1.3-12.5 mg/kg x 5 iv administrations. Negative results on chromosomal aberration test and in vitro micronucleus test suggest that compound 8 is a hopeful candidate for visceral leishmaniasis (VL).
Subject(s)
Antiprotozoal Agents/pharmacology , Benzothiazoles/pharmacology , Leishmania donovani/drug effects , Leishmaniasis, Visceral/drug therapy , Animals , Antiprotozoal Agents/chemistry , Benzothiazoles/chemistry , Cell Line , Cell Survival/drug effects , Female , Macrophages/drug effects , Mice , Mice, Inbred BALB C , Parasitic Sensitivity Tests , RatsABSTRACT
Selected members of three classes of rhodacyanine dyes, [0,0]-, [1,0]-, and [0,0,0]-rhodacyanines, were synthesized and their in vitro antimalarial activities against Plasmodium falciparum K1 (chloroquine-resistant strain) as well as their in vivo activities against P. berghei in mice were determined. The novel [0,0,0]-rhodacynines, 3e and 3h, possessing a benzothiazole moiety, were shown to have highly promising antimalarial activities in vivo. Moreover, the [0,0,0]-rhodacyanines were found to be orally bioavailable.
