BackgroundThe early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to Mycobacterium tuberculosis (Mtb).MethodsPubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.ResultsWe retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.ConclusionmiRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance. Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).

Peptide therapeutics have recently gained momentum in antiviral therapy due to their increased potency and cost-effectiveness. Interaction of the HIV-1 envelope gp120 with the host CD4 receptor is a critical step for viral entry, and therefore the CD4-binding site (CD4bs) of gp120 is a potential hotspot for blocking HIV-1 infection. The present study aimed to design short peptides from well-characterized CD4bs targeting broadly neutralizing antibodies (bNAbs), which could be utilized as bNAb mimetics for viral neutralization. Co-crystallized structures of HIV-1 gp120 in complex with CD4bs-directed bNAbs were used to derive hexameric peptides using the Rosetta Peptiderive protocol. Based on empirical insights into co-crystallized structures, peptides derived from the heavy chain alone were considered. The peptides were docked with both HIV-1 subtype B and C gp120, and the stability of the peptide–antigen complexes was validated using extensive Molecular Dynamics (MD) simulations. Two peptides identified in the study demonstrated stable intermolecular interactions with SER365, GLY366, and GLY367 of the PHE43 cavity in the CD4 binding pocket, and with ASP368 of HIV-1 gp120, thereby mimicking the natural interaction between ASP368gp120 and ARG59CD4–RECEPTOR. Furthermore, the peptides featured favorable physico-chemical properties for virus neutralization suggesting that these peptides may be highly promising bNAb mimetic candidates that may be taken up for experimental validation.