Coronavirus pandemic has caused a vast number of deaths worldwide. Thus creating an urgent need to develop effective counteragents against novel coronavirus disease (COVID-19). Many antiviral drugs have been repurposed for treatment but implicated minimal recovery, which further advanced the need for clearer insights and innovation to derive effective therapeutics. Strategically, Noscapine, an approved antitussive drug with positive effects on lung linings may show favorable outcomes synergistically with antiviral drugs in trials. Hence, we have theoretically examined the combinatorial drug therapy by culminating the existing experimental results with in silico analyses. We employed the antitussive noscapine in conjugation with antiviral drugs (Chloroquine, Umifenovir, Hydroxychloroquine, Favlplravir and Galidesivir). We found that Noscapine-Hydroxychloroquine (Nos-Hcq) conjugate has strong binding affinity for the main protease (Mpro) of SARS-CoV-2, which performs key biological function in virus infection and progression. Nos-Hcq was analyzed through molecular dynamics simulation. The MD simulation for 100 ns affirmed the stable binding of conjugation unprecedentedly through RMSD and radius of gyration plots along with critical reaction coordinate binding free energy profile. Also, dynamical residue cross-correlation map with principal component analysis depicted the stable binding of Nos-Hcq conjugate to Mpro domains with optimal secondary structure statistics of complex dynamics. Also, we reveal the drugs with stable binding to major domains of Mpro can significantly improve the work profile of reaction coordinates, drug accession and inhibitory regulation of Mpro. The designed combinatorial therapy paves way for further prioritized in vitro and in vivo investigations for drug with robust binding against Mpro of SARS-CoV-2.

Graphene oxide (GO) has attracted much attention in the past few years because of its interesting and promising electrical, thermal, mechanical, and structural properties. These properties can be altered, as GO can be readily functionalized. Brodie synthesized the GO in 1859 by reacting graphite with KClO 3 in the presence of fuming HNO 3 ; the reaction took 3−4 days to complete at 333 K. Since then, various schemes have been developed to reduce the reaction time, increase the yield, and minimize the release of toxic byproducts (NO 2 and N 2 O 4 ). The modified Hummers method has been widely accepted to produce GO in bulk. Due to its versatile characteristics, GO has a wide range of applications in different fields like tissue engineering, photocatalysis, catalysis, and biomedical applications. Its porous structure is considered appropriate for tissue and organ regeneration. Various branches of tissue engineering are being extensively explored, such as bone, neural, dentistry, cartilage, and skin tissue engineering. The band gap of GO can be easily tuned, and therefore it has a wide range of photocatalytic applications as well: the degradation of organic contaminants, hydrogen generation, and CO 2 reduction, etc. GO could be a potential nanocarrier in drug delivery systems, gene delivery, biological sensing, and antibacterial nanocomposites due to its large surface area and high density, as it is highly functionalized with oxygen-containing functional groups. GO or its composites are found to be toxic to various biological species and as also discussed in this review. It has been observed that superoxide dismutase (SOD) and reactive oxygen species (ROS) levels gradually increase over a period after GO is introduced in the biological systems. Hence, GO at specific concentrations is toxic for various species like earthworms, Chironomus riparius, Zebrafish, etc.

Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and cloned into type 5 adenovirus. PCA3-3STA activity was highly specific for PCa cells, ranging between 98.7- and 108.0-fold higher than that for benign primary prostate epithelial or non-PCa cells, respectively. In human PCa xenografts, PCA3-3STA displayed robust bioluminescent signals at levels that are sufficient to translate to positron emission tomography (PET)-based reporter imaging. Remarkably, when freshly isolated benign or cancerous prostate biopsies were infected with PCA3-3STA, the optical signal produced from primary PCa biopsies was significantly higher than from benign prostate biopsies (4.4-fold, p < 0.0001). PCA3-3STA therefore represents a PCa-specific expression system with the potential to target, with high accuracy, primary or metastatic PCa epithelial cells for imaging, vaccines, or gene therapy.

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Since December 2019, the humanity is in trouble due to the huge infection of SARS‐CoV‐2 and caused COVID‐19, named by WHO. Therefore, researchers and health care organizations are using the repurposing drugs against the infection by this new coronavirus. Acyclovir and ganciclovir are the drugs used in the cure of infection due to herpes virus so the impact of these drugs along with the designed ionic liquids individually as well as in combination against the Mpro of nCoV was investigated using molecular docking. The drugs {acyclovir (1) and ganciclovir (2)}, ionic liquids (A, B, and C), and their combinations (1‐A, 1‐B, 1‐C, 2‐A, 2‐B, and 2‐C) were studied using density functional theory (DFT) calculations via determining the different energies. These values are important to understand the formation of 1‐A, 1‐B, 1‐C, 2‐A, 2‐B, and 2‐C and are found to negative. Complexes formed by acyclovir with ILs (B and C) are more favorable due to less value of change in free energy. Further, 1 interacts with IL(C) and 2 interacts well with IL(A), and it is based on the calculated dipole moment of 1‐C and 2‐A, as 17.4 and 27.6, respectively. Therefore, it can be considered as more polar and more water soluble. Results revealed that complex 2‐A found to more stable than 1‐A and showed the best binding energy of −149 kcal/mol against the Mpro of nCoV. It indicates that the drug, ganciclovir (2) in presence of the IL(A) binds effectively with the Mpro of nCoV instead independently.

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Cancer cell heterogeneity is well-documented. Therefore, techniques to monitor single cell heterogeneous responses to treatment are needed. We developed a highly translational and quantitative bioluminescence microscopy method to measure single cell androgen receptor (AR) activity modulation by antiandrogens from fluid biopsies. We showed that this assay can detect heterogeneous cellular response to drug treatment and that the sum of single cell AR activity can mirror the response in the whole cell population. This method may thus be used to monitor heterogeneous dynamic treatment responses in cancer cells.

Background: Aberrant androgen receptor (AR) signaling is a major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance in prostate cancer. Heat shock protein 27 (Hsp27) is a molecular chaperone that is activated in response to heat shock and hypoxia. Hsp27 has previously been reported to facilitate AR nuclear translocation in a p38 mitogen-activated protein kinase (MAPK) dependent manner in castration-sensitive prostate cancer cell lines. Here, we evaluated the potential for inhibiting p38 MAPK/Hsp27 mediated AR signaling under normoxia and hypoxia in experimental models of CRPC. Methods: We inhibited p38 MAPK with SB203580 in prostate cancer cell lines and measured Hsp27 phosphorylation, AR activity, cell proliferation, and clonogenicity under normoxia and hypoxia. AR activity was measured using an androgen response element driven reporter assay and qPCR to measure expression of AR target genes. Xenograft-bearing mice were treated with SB203580 to measure tumor growth and serum prostate specific antigen (PSA). Results: Our results indicate that p38 MAPK and Hsp27 are activated under normoxia and hypoxia in response to androgens in CRPC cells. p38 MAPK inhibition diminished Hsp27 activation and the hypoxia-mediated increase in AR activity. Additionally, inhibition of p38 MAPK activity decreased proliferation and survival of CRPC cells in vitro and prolonged the survival of tumor-bearing mice. Conclusions: These results suggest that p38 MAPK inhibition may represent a therapeutic strategy to disrupt AR signaling in the heterogeneous CRPC tumor microenvironment.