ROTHAN, H. | Search bioRxiv

bioRxiv2020

Evaluation of neutralizing antibodies produced by papaya mosaic virus nanoparticles fused to the E2EP3 peptide epitope of Chikungunya envelope

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV E2EP3, and E2EP3 PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3 PapMV and PapMV E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3 PapMV or PapMV E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.

microbiology↗

bioRxiv2019

Novel Quinazoline derivatives inhibited HCV Serine protease and viral replication in Huh-7 cells.

Drugs against HCV infection are facing several drawbacks such as undesirable side effects, emerging of HCV resistant strains, and high cost of the entire course of treatment. Thus, new active and cost-effective compounds are required to develop effective drugs to combat HCV infection. This study was designed to test the antiviral activity of quinazoline derivatives against HCV infection using HCV protease assay (HCV NS3-4Apro) and cell-based HCV replicon assay. The results showed that some of quinazoline derivatives inhibited HCV NS3-4Apro with IC50 ranged from 42 {micro}M of compound 4 to 150 {micro}M of compound 2. In this study, compound 4 was considered as the best compound lead to developing potent anti-HCV NS3-4Apro inhibitors. The toxic dose of compound 4 was more than 80 {micro}M for 24, 48, and 72 h. Compound 4 showed dose-dependent inhibition against HCV replication with a considerable reduction in Rluc activity at 40 {micro}M. This finding was further investigated by immunostaining that showed the inhibitory effect of compound 4 against HCV NS3-4Apro was dose-dependent. This study identified a unique small molecule compound that could lead to the development of HCV NS3-A4pro inhibitors and would be useful to develop highly effective drugs for HCV infection based on HCV NS3-4A protease inhibition.

microbiology↗