Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex.

The entry of the SARS-CoV-2, a causative agent of COVID-19, into human host cells is mediated by the SARS-CoV-2 spike (S) glycoprotein, which critically depends on the formation of complexes involving the spike protein receptor-binding domain (RBD) and the human cellular membrane receptor angiotensin-converting enzyme 2 (hACE2). Using classical site density functional theory (SDFT) and structural bioinformatics methods, we investigate binding and conformational properties of these complexes and study the overlooked role of water-mediated interactions. Analysis of the three-dimensional reference interaction site model (3DRISM) of SDFT indicates that water mediated interactions in the form of additional water bridges strongly increases the binding between SARS-CoV-2 spike protein and hACE2 compared to SARS-CoV-1-hACE2 complex. By analyzing structures of SARS-CoV-2 and SARS-CoV-1, we find that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) has expanded in size, indicating large conformational change relative to SARS-CoV-1 S protein. Protomer with the up-conformational form of RBD, which binds with hACE2, exhibits stronger intermolecular interactions at the RBD-ACE2 interface, with differential distributions and the inclusion of specific H-bonds in the CoV-2 complex. Further interface analysis has shown that interfacial water promotes and stabilizes the formation of CoV-2/hACE2 complex. This interaction causes a significant structural rigidification of the spike protein, favoring proteolytic processing of the S protein for the fusion of the viral and cellular membrane. Moreover, conformational dynamics simulations of RBD motions in SARS-CoV-2 and SARS-CoV-1 point to the role in modification of the RBD dynamics and their impact on infectivity.

Holistic Care Approach for the Effective Management of Severe Radiation Dermatitis Using Neem (Azadirachta indica) and Honey after Head-and-Neck Radiotherapy.

Head and neck cancer is the eighth common type among all cancer types around the world. Its treatment comprises surgery, radiation therapy, chemotherapy and /or a combination of restoration therapy and social support Conventional fraction size ranges from 1.8 to 3 Grays (Gy) per fraction over 4-6 weeks. The accumulative dose of radiation for the primary treatment of head and neck cancer treatment is 60 to 70 Gy, depending on the irradiation of the tumor. Ionizing Radiotherapy is used along with concurrent chemotherapy which is the standard treatment in locally advanced head and neck cancers. Radiation treatment is commonly delivered in the form of high energy photons through an external beam. These results in ionization of electrons that cause direct strand breaks of cellular DNA and the release of free radicals, resulting in cellular damage to both normal and tumor cells. Radiation disrupts the normal process of wound healing at various stages.

Challenges Encountered in Placement of Ostomy Bag for Palliative Care in a Patient with Colorectal Cancer.

Fecal fistula develop in patients with cancer associated with difficult management situation, which is often complicated by prior treatment including surgery, radiation therapy, and chemotherapy. Affecting factors such as timing of additional adjuvant therapy or palliative care, technical considerations for operating on irradiated bowel, poor wound healing, increased risk of additional fecal fistula, and decreased likelihood of spontaneous fecal fistula closure all need to be considered in this scenario. Here, the authors focus specifically on the management of fecal fistula associated with cancer and/or radiation- induced injury to the bowel.