Interactive Mechanism of Potential Inhibitors with Glycosyl for SARS-CoV-2 by Molecular Dynamics Simulation

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a type of Ribonucleic Acid (RNA) coronavirus and it has infected and killed many people around the world. It is reported that the receptor binding domain of the spike protein (S_RBD) of the SARS-CoV-2 virus is responsible for attachment to human angiotensin converting enzyme II (ACE2). Many researchers are attempting to search potential inhibitors for fighting SARS-CoV-2 infection using theoretical or experimental methods. In terms of experimental and theoretical research, Cefuroxime, Erythromycin, Lincomycin and Ofloxacin are the potential inhibitors of SARS-CoV-2. However, the interactive mechanism of the protein SARS-CoV-2 and the inhibitors are still elusive. Here, we investigated the interactions between S_RBD and the inhibitors using molecular dynamics (MD) simulations. Interestingly, we found that there are two binding sites of S_RBD for the four small molecules. In addition, our analysis also illustrated that hydrophobic and π-π stacking interactions play crucial roles in the interactions between S_RBD and the small molecules. In our work, we also found that small molecules with glycosyl group have more effect on the conformation of S_RBD than other inhibitors, and they are also potential inhibitors for the genetic variants of SARS-CoV-2. This study provides in silico-derived mechanistic insights into the interactions of S_RBD and inhibitors, which may provide new clues for fighting SARS-CoV-2 infection.

PreDTIs: prediction of drug-target interactions based on multiple feature information using gradient boosting framework with data balancing and feature selection techniques.

Discovering drug-target (protein) interactions (DTIs) is of great significance for researching and developing novel drugs, having a tremendous advantage to pharmaceutical industries and patients. However, the prediction of DTIs using wet-lab experimental methods is generally expensive and time-consuming. Therefore, different machine learning-based methods have been developed for this purpose, but there are still substantial unknown interactions needed to discover. Furthermore, data imbalance and feature dimensionality problems are a critical challenge in drug-target datasets, which can decrease the classifier performances that have not been significantly addressed yet. This paper proposed a novel drug-target interaction prediction method called PreDTIs. First, the feature vectors of the protein sequence are extracted by the pseudo-position-specific scoring matrix (PsePSSM), dipeptide composition (DC) and pseudo amino acid composition (PseAAC); and the drug is encoded with MACCS substructure fingerings. Besides, we propose a FastUS algorithm to handle the class imbalance problem and also develop a MoIFS algorithm to remove the irrelevant and redundant features for getting the best optimal features. Finally, balanced and optimal features are provided to the LightGBM Classifier to identify DTIs, and the 5-fold CV validation test method was applied to evaluate the prediction ability of the proposed method. Prediction results indicate that the proposed model PreDTIs is significantly superior to other existing methods in predicting DTIs, and our model could be used to discover new drugs for unknown disorders or infections, such as for the coronavirus disease 2019 using existing drugs compounds and severe acute respiratory syndrome coronavirus 2 protein sequences.

Radiotherapy workflow and protection procedures during the Coronavirus Disease 2019 (COVID-19) outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China.

The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis.

Radiation Therapy Care During a Major Outbreak of COVID-19 in Wuhan.

PURPOSE: The epidemic of coronavirus disease 2019 (COVID-19) challenges the prevention and protection of the cancer patients and the staff in the department of radiation oncology. METHODS: At the Hubei Cancer Hospital, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. RESULTS: Radiation therapy treatments were resumed on January 30th and have never stopped again at the hospital regardless of the circumstances of the ongoing outbreak. Between January 30th and the time of the writing, we have treated over 100 radiation therapy patients, with no incidence of on-site COVID-19 transmission between patients and health care workers in the duration. CONCLUSIONS: Our experience will help guide the practice in other regions that are or might be facing outbreaks of this disease.