Respiratory infections by RNA viruses are one of the major burdens on global health and economy. Viruses like influenza or coronaviruses can be transmitted through respiratory droplets or contaminated surfaces. An effective antiviral coating can decrease the viability of the virus particles in our surroundings significantly, hence reducing their transmission rate. Here, we have screened a series of nanoparticles and their composites for antiviral activity using a nanoluciferase-based highly sensitive influenza A reporter virus. We have identified copper–graphene (Cu–Gr) nanocomposite as a material with strong antiviral activity. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide-embedded graphene sheet architecture that can inactivate the virion particles within 30 min of preincubation and subsequently interferes with the entry of these virion particles into the host cell. This ultimately results in reduced viral gene expression, replication and production of progeny virus particles, and thereby slowing down of the overall pace of progression of infection. Using poly(vinyl alcohol) (PVA) as a capping agent, we have been able to generate a Cu–Gr nanocomposite-based highly transparent coating that retains its original antiviral activity in the solid form and hence can be potentially implemented on a wide variety of surfaces to minimize the transmission of respiratory virus infections.
Accurate diagnosis with secure and target-specific drug delivery improves the success rate in cancer treatment and patient survival outcomes. The development of stimuli-responsive theranostic with the molecular computing ability could address all these criteria at a time. This work attempts to design a multifunctional biocomputing agent that can serve as a secure and target-specific drug carrier and simultaneously act as a molecular logic device. Hence, we developed holmium-doped carbon dot-gelatin nanoparticles (HoCDGNPs) by two-step desolvation methods and used them as fluorescence (FL) imaging and MRI contrast agents with effective pH and Cu 2+ ion sensing ability. Furthermore, Boolean algebraic operations (NOR, OR, IMP, and NIMP) are executed on the HoCDGNP system using the FL/magnetic resonance (MR) response in the presence of different inputs (H + , OH − , and Cu 2+ ions), and the results are mesmerizing. Moreover, the FL quenching phenomena of HoCDGNPs in the presence of Cu 2+ ions by cupricamine or cupric-carboxylate coordination formation are also exploited in the living HeLa cells. Finally, the resulting system is used for pH-responsive drug delivery of a model anticancer drug (5-fluorouracil), and the release profile is found selective and sustained over the pH range 6−7.4. Thus, it counters the shortcomings associated with the 5-fluorouracil drug administration (short lifetime and poor specificity at high doses). The cellular uptake and cell viability assessment are also accomplished in cancerous and noncancerous cell lines to ensure the acceptability of this multifunctional biocomputing system, and the results are pretty satisfactory.
As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key towards sustenance. Here, we identify an evolutionary conserved “E-L-L” motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing its post-fusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduces the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this “E-L-L” motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the “E-L-L” motif rendered the protein completely resistant to the drug, establishing its specificity towards this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective towards all major variants of concerns of SARS-CoV-2 including beta, kappa, delta, and omicron. Together, we show that this conserved essential “E-L-L” motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.
Respiratory infections by RNA viruses are one of the major burdens upon global health and economy. Viruses like influenza or coronaviruses can be transmitted through respiratory droplets or contaminated surfaces. An effective antiviral coating can decrease the viability of the virus particles in the outside environment significantly, hence reducing their transmission rate. In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Using this screening system, we have identified copper-graphene (Cu-Gr) nanocomposite shows strong antiviral activity. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This ultimately results in reduced viral gene expression, replication and production of progeny virus particles, slowing down the overall pace of progression of infection. Using PVA as a capping agent, we have been able to generate a Cu-Gr nanocomposite based highly transparent coating that retains its original antiviral activity in the solid form.
The efficient monitoring and early detection of viruses may provide essential information about the disease. In this work, we have highlighted the interaction between DNA and a two-dimensional (2D) metal...
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