RESUMO
The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.
Assuntos
Antivirais/farmacologia , Canabidiol/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Células A549 , Animais , Antivirais/química , COVID-19/virologia , Canabidiol/química , Canabidiol/metabolismo , Chlorocebus aethiops , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/genética , Endorribonucleases/metabolismo , Células Epiteliais/virologia , Feminino , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Interferons/metabolismo , Camundongos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , SARS-CoV-2/fisiologia , Células Vero , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Molecular Assemblies Including Nucleic Acids for Functional Materials and Systems The original and fundamental function of nucleic acids is to store the genetic information required to synthesize proteins. Since mRNA encodes the amino acid sequence of the protein to be expressed, it is attracting attention as biomedical material exemplified as a vaccine against SARS-CoV-2. During the fibrin gel formation by the catalytic activity of thrombin, the thrombin aptamer unit enables the internalization of bApt into fibrin gel. Since another aptamer unit, which is interacting with the drug molecule, can be easily exchanged depending on the therapeutic target, the assembled fibrin gel can be a biocompatible material that stores and releases various drug molecules [7]. [...]the assembly of Puf family proteins on the 3′ untranslated region of mRNA affects protein expression. Since the target RNA sequence of the Puf family proteins can be altered by rationally designing amino acids in their RNA binding domain, a strategy that assembles multiple Puf proteins on target mRNA would enable the efficient regulation of protein expression. Since the strong suppression was observed only when the four types of TTP-PUF fusion proteins are present as it is like a logic gate, the technology is expected to be applied as a gene regulation tool in the field of synthetic biology.