Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis—this poses challenges for effective surgical control and future tumor-related mortality. There are numerous diagnostic methods that can be used to reduce the risk of colorectal carcinoma. Among these, targeted nanotherapy aims to eliminate the tumor and any metastasis. Active targeting can increase the effectiveness and quantity of drugs delivered to the target site. Antibodies that target overexpressed receptors on cell surfaces and indicators are coupled with drug-loaded carriers. The major target receptors of chemotherapeutic drugs delivery include VEGFR, EGFR, FGFR, HER2, and TGF. On account of its major and diverse roles in cancer, it is important to target EGFR in particular for better tumor selection, as EGFR is overexpressed in 25 to 82% of colorectal carcinoma cases. The EGFR monoclonal immunoglobulins cetuximab/panitumumab can thus be used to treat colorectal cancer. This review examines carriers that contain cetuximab-conjugated therapeutic drugs as well as their efficacy in anticancer activities.

The ongoing global outbreak of new corona virus (SARS-CoV-2) has been recognized as global public health concern since it causes high morbidity and mortality every day. Due to the rapid spreading and re-emerging, we need to find a potent drug against SARS-CoV-2. Synthetic drugs, such as hydroxychloroquine, remdisivir have paid more attention and the effects of these drugs are still under investigation, due to their severe side effects. Therefore, the aim of the present study was performed to identify the potential inhibitor against main protease SARS-CoV-2 6LU7. In this study, RO5, ADME properties, molecular dynamic simulations and free binding energy prediction were mainly investigated. The molecular docking study findings revealed that andrographolide had higher binding affinity among the selected natural diterpenoids compared to co-crystal native ligand inhibitor N3. The persistent inhibition of Ki for diterpenoids was analogous. Furthermore, the simulations of molecular dynamics and free binding energy findings have shown that andrographolide possesses a large amount of dynamic properties such as stability, flexibility and binding energy. In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (M^pro). However, preclinical and clinical trials are needed for the further scientific validation before use.

Traditional cancer treatments have posed numerous obstacles, including toxicity, multiple drug resistance, and financial cost. On the contrary, bioactive phytochemicals used in complementary alternative medicine have recently increased attention due to their potential to modulate a wide range of molecular mechanisms with a less toxic effect. Therefore, we investigated the potential regulatory mechanisms of andrographolide to treat colorectal cancer (CRC) using a network pharmacology approach. Target genes of andrographolide were retrieved from public databases (PharmMapper, Swiss target prediction, Targetnet, STITCH, and SuperPred), while targets related to CRC were retrieved from disease databases (Genecards and DisGeNet) and expression datasets (GSE32323 and GSE8671) were retrieved from gene expression omnibus (GEO). Protein-protein interaction networks (PPI) were generated using STRING and Cytoscape, and hub genes were identified by topology analysis and MCODE. Annotation of target proteins was performed using Gene Ontology (GO) database DAVID and signaling pathway enrichment analysis using the Kyoto Encyclopedia and Genome Database (KEGG). Survival and molecular docking analysis for the hub genes revealed three genes (PDGFRA, PTGS2, and MMP9) were involved in the overall survival of CRC patients, and the top three genes with the lowest binding energy include PDGFRA, MET, and MAPK1. MET gene upregulation and PDGFRA and PTGS2 gene downregulation are associated with the survival of CRC patients, as revealed by box plots and correlation analysis. In conclusion, this study has provided the first scientific evidence to support the use of andrographolide to inhibit cellular proliferation, migration, and growth, and induce apoptosis by targeting the hub genes (PDGFRA, PTGS2, MMP9, MAPK1, and MET) involved in CRC migration and invasion.