Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury.

OBJECTIVE: This research aims to study the target specificity of selective bioactive compounds in complexing with the human angiotensin-converting enzyme (hACE2) receptor to impede the severe acute respiratory syndrome coronavirus 2 influx mechanism resulting in cardiac injury and depending on the receptor's active site properties and quantum tunneling. MATERIALS AND METHODS: A library of 120 phytochemical ligands was prepared, from which 5 were selected considering their absorption, distribution, metabolism, and excretion (ADMET) and quantitative structure-activity relationship (QSAR) profiles. The protein active sites and belonging quantum tunnels were defined to conduct supramolecular docking of the aforementioned ligands. The hydrogen bond formation and hydrophobic interactions between the ligand-receptor complexes were studied following the molecular docking steps. A comprehensive molecular dynamic simulation (MDS) was conducted for each of the ligand-receptor complexes to figure out the values - root mean square deviation (RMSD) (Å), root mean square fluctuation (RMSF) (Å), H-bonds, Cα, solvent accessible surface area (SASA) (Å2), molecular surface area (MolSA) (Å2), Rg (nm), and polar surface area (PSA) (Å). Finally, computational programming and algorithms were used to interpret the dynamic simulation outputs into their graphical quantitative forms. RESULTS: ADMET and QSAR profiles revealed that the most active candidates from the library to be used were apigenin, isovitexin, piperolactam A, and quercetin as test ligands, whereas serpentine as the control. Based on the binding affinities of supramolecular docking and the parameters of molecular dynamic simulation, the strength of the test ligands can be classified as isovitexin > quercetin > piperolactam A > apigenin when complexed with the hACE2 receptor. Surprisingly, serpentine showed lower affinity (-8.6 kcal/mol) than that of isovitexin (-9.9 kcal/mol) and quercetin (-8.9 kcal/mol). The MDS analysis revealed all ligands except isovitexin having a value lower than 2.5 Ǻ. All the test ligands exhibited acceptable fluctuation ranges of RMSD (Å), RMSF (Å), H-bonds, Cα, SASA (Å2), MolSA (Å2), Rg (nm), and PSA (Å) values. CONCLUSION: Considering each of the parameters of molecular optimization, docking, and dynamic simulation interventions, all of the test ligands can be suggested as potential targeted drugs in blocking the hACE2 receptor.

COVID-19 Infection in Pregnancy: A Review.

Coronavirus disease 2019 (COVID-19), which is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world's demographics, resulting in more than 3.8 million deaths worldwide and establishing itself as the most serious global health crisis since the 1918 influenza pandemic. Several questions remain unanswered regarding the effects of COVID-19 disease during pregnancy. Although most infections are mild in high-risk populations, the severe disease frequently leads to intubation, intensive care unit admission, and, in some cases, death. Hormonal and physiological changes in the immune and respiratory systems, cardiovascular function, and coagulation may affect the progression of COVID-19 disease in pregnancy. However, the consequences of coronavirus infection on implantation, fetal growth and development, labor, and newborn health have yet to be determined, and, consequently, a coordinated global effort is needed in this respect. Principles of management concerning COVID-19 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and co-infection, fetal and uterine contraction monitoring, prevention, and / or treatment of thromboembolism early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. This review focuses on COVID-19 during pregnancy, its management, and the area where further investigations are needed to reduce the risk to mothers and their newborns.

Immunoinformatics-guided design of an epitope-based vaccine against severe acute respiratory syndrome coronavirus 2 spike glycoprotein.

AIMS: With a large number of fatalities, coronavirus disease-2019 (COVID-19) has greatly affected human health worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19. The World Health Organization has declared a global pandemic of this contagious disease. Researchers across the world are collaborating in a quest for remedies to combat this deadly virus. It has recently been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator by which the virus enters host cells. MAIN METHODS: Our group comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis and a phylogenetic analysis. We predicted the strongest immunogenic epitopes of the SGP for both B cells and T cells. KEY FINDINGS: We focused on predicting peptides that would bind major histocompatibility complex class I. Two optimal epitopes were identified, WTAGAAAYY and GAAAYYVGY. They interact with the HLA-B*15:01 allele, which was further validated by molecular docking simulation. This study also found that the selected epitopes are able to be recognized in a large percentage of the world's population. Furthermore, we predicted CD4+ T-cell epitopes and B-cell epitopes. SIGNIFICANCE: Our study provides a strong basis for designing vaccine candidates against SARS-CoV-2. However, laboratory work is required to validate our theoretical results, which would lay the foundation for the appropriate vaccine manufacturing and testing processes.