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Biology subjects

Ng, L. F. P.

Publications and source records attributed to Ng, L. F. P..

3 recordsLinked to original sources

A broad-spectrum, biocompatible, virucidal polymer reduces chikungunya virus in murine models

Autochthonous transmission of arboviruses poses significant threats to global health and economies. Yet, no effective antivirals exist. Building on our previous antiviral star-polymer, we designed zwitterionic star-polymers for efficacy in high protein environments. A polymer with 12% positively charged monomer (Zwitterionic Polymer-ZP12) exhibited broad-spectrum, biocompatible antiviral activity against Alphaviridae, Flaviviridae, Herpesviridae, and Picornaviridae. Using murine models for Chikungunya virus (CHIKV) infection, ZP12 treatment (10 mg/kg every 24 hours for 7 days) reduced tissue viral load by 90% 3 days post-infection and significantly alleviated CHIKV-induced joint swelling. Mechanistically, ZP12 downregulated CHIKV-driven immunopathogenesis by reducing viral load and dampening CD4+ T cell and macrophage activation in virus-infected joints. With no current antiviral interventions for these arboviruses, ZP12 represents a promising intervention for combating future pandemics.

microbiology↗

Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant.

The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.

immunology↗

Novel differential linear B-cell epitopes to identify Zika and dengue virus infections in patients

BackgroundRecent Zika virus (ZIKV) outbreaks challenged existing laboratory diagnostic standards, especially for serology-based methods. Due to the genetic and structural similarity of ZIKV with other flaviviruses, this results in cross-reactive antibodies which confounds serological interpretations.\n\nMethodsPlasma from Singapore ZIKV patients was screened longitudinally for antibody responses and neutralizing capacities against ZIKV. Samples from healthy controls, ZIKV and DENV patients were further assessed using ZIKV and DENV peptides of precursor membrane (prM), envelope (E) or non-structural 1 (NS1) viral proteins in a peptide-based ELISA for epitope identification. Identified epitopes were re-validated and diagnostically evaluated using sera of patients with DENV, bacteria or unknown infections from Thailand.\n\nResultsLong-lasting ZIKV-neutralizing antibodies were elicited during ZIKV infection. Thirteen potential linear B-cell epitopes were identified and of these, four common flavivirus, three ZIKV-specific, and one DENV-specific differential epitopes had more than 50% sensitivities and specificities. Notably, ZIKV-specific peptide 26 on domain I/II of E protein (amino acid residues 271-288) presented 80% sensitivity and 85.7% specificity. Importantly, the differential epitopes also showed significance in differentiating non-flavivirus patient samples.\n\nConclusionsLinear B-cell epitope candidates to differentiate ZIKV and DENV infections were identified, providing the first step towards the design of a much-needed serology-based assay.

immunology↗