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nuates microglial activation and downregulates the concentrations of pro-inflammatory mediators in pneumococcal infection

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. However, we didn't observe a reduction in cortical or hippocampal injury. This data provides evidence that inhibition of microglia by adjuvant CB2 agonists therapy effectively downmodulates neuroinflammation but does not reduce brain damage in experimental pneumococcal meningitis.

JWH-133 attenuates microglial activation and downregulates the concentrations of pro-inflammatory mediators in pneumococcal infection in vitro and in vivo. However, we didn't observe a reduction in cortical or hippocampal injury. This data provides evidence that inhibition of microglia by adjuvant CB2 agonists therapy effectively downmodulates neuroinflammation but does not reduce brain damage in experimental pneumococcal meningitis.COVID-19, the human coronavirus disease caused by SARS-CoV-2, was reported for the first time in Wuhan, China in late 2019. COVID-19 has no preventive vaccine or proven standard pharmacological treatment, and consequently, the outbreak swiftly became a pandemic affecting more than 215 countries around the world. For the diagnosis of COVID-19, the only reliable diagnostics is a qPCR assay. Among other diagnostic tools, the CRISPR-Cas system is being investigated for rapid and specific diagnosis of COVID-19. The CRISPR-Cas-based methods diagnose the SARS-CoV-2 infections within an hour. Apart from its diagnostic ability, CRISPR-Cas system is also being assessed for antiviral therapy development; however, till date, no CRISPR-based therapy has been approved for human use. The Prophylactic Antiviral CRISPR in huMAN cells (PAC-MAN), which is Cas 13 based strategy, has been developed against coronavirus. Although this strategy has the potential to be developed as a therapeutic modality, it may face significant challenges for approval in human clinical trials. This review is focused on describing potential use and challenges of CRISPR-Cas based approaches for the development of rapid and accurate diagnostic technique and/or a possible therapeutic alternative for combating COVID-19. The assessment of potential risks associated with use of CRISPR will be important for future clinical advancements.Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models.Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.Hemorrhagic fever with renal syndrome (HFRS) is the most common natural focal disease in the Russian Federation with about 6-12 thousand cases annually. 97.7% of all HFRS cases in Russia are caused by the Puumala virus, 1.5%-by the Hantaan, Amur, Seoul viruses, and about 0.8% by the Kurkino and Sochi viruses. There are no licensed vaccines for the prevention of HFRS in the European Region; there are no specific therapeutic to treat orthohantavirus infections. Here we report the results of candidate polyvalent HFRS vaccine preclinical studies. The vaccine was produced on the basis of three viruses Puumala, strain PUU-TKD/VERO, Hantaan, strain HTN-P88/VERO, and Sochi, strain DOB-SOCHI/VERO. Resatorvid cost These viruses were inactivated with β-propiolacton, purified by gel filtration and aluminum hydroxide adsorbed. 18-20 g female BALB/c mice were immunized intramuscularly 2 or 3 times with a 2-week intervals and blood was taken 2 weeks after immunization. FRNT50 performed for virus specific antibodies determination. ELISA kits (Bender MedSystems, Cusabio) were used for detection of cytokines IL-1β, IL-12, INF-ɣ. Neutralizing antibodies geometric mean titers to the Puumala, Hantaan, and Sochi viruses were 9.22 ± 0.31, 9.17 ± 0.26, 8.96 ± 0.34 log2/ml. Up to 1/32 vaccine dilution neutralizing antibodies were identified in 10/10 immunized mice with titers ≥ 3,32 log2/ml. IL-12 and INF-ɣ increased after immunization in average 5.5 and 2.8 times respectively, that reflects the Th1 type immunity stimulation. IL-1β slightly increased, that may suggest vaccine low reactogenicity. According to our preclinical investigations, the candidate polyvalent HFRS vaccine elicits balanced immune response to the Puumala, Hantaan and Sochi viruses.